Clinical inertia to insulin initiation and intensification in the UK: A focused literature review

  • Kamlesh Khunti
    Correspondence
    Corresponding author at: Diabetes Research Centre, College of Medicine, Biological Sciences & Psychology, University of Leicester, Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK. Tel.: +44 116 258 4005. fax: +44 116 258 4053.
    Affiliations
    Leicester Diabetes Centre, University of Leicester, UK
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  • David Millar-Jones
    Affiliations
    Royal Gwent Hospital and Oak Street Surgery, Cwmbran, UK
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Open AccessPublished:October 07, 2016DOI:https://doi.org/10.1016/j.pcd.2016.09.003

      Highlights

      • Timely achievement of glycaemic control is key to optimising clinical outcomes.
      • Clinical inertia is most pronounced at the intensification with insulin stage.
      • The NICE guidelines on type 2 diabetes do not explicitly address clinical inertia.
      • Barriers to treatment intensification span patient, clinician and system levels.
      • Clinical inertia can be tackled with increased education on therapeutic options.

      Abstract

      Achieving tight glycaemic control early following the diagnosis of type 2 diabetes is key to optimising clinical outcomes, yet many patients and clinicians are reluctant to initiate and intensify insulin therapy. Reasons for this arise primarily from a lack of time, clinical expertise and patient understanding. However, meaningful progress can be achieved with self-management educational programmes soon after diagnosis. Clinician education and training, along with easy-to-use and well-tolerated therapies (for example, those carrying a low risk of hypoglycaemia and/or avoiding weight gain), may also increase the likelihood of patient adherence.

      Keywords

      1. Introduction

      Currently, 387 million people worldwide are living with diabetes, of whom 3.9 million are in the UK [
      • Diabetes UK
      Diabetes Facts and Stats Version 4, Revision May.
      ]. The majority remain in poor glycaemic control and at risk of vascular complications, which may already be developing at the time of diagnosis [
      • Inzucchi S.E.
      • Bergenstal R.M.
      • Buse J.B.
      • et al.
      Management of hyperglycemia in type 2 diabetes: 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes.
      ,

      NICE guideline (December 2015), Type 2 Diabetes in Adults: Management (NG28). Available at: https://www.nice.org.uk/guidance/ng28/resources/type-2-diabetes-in-adults-management-1837338615493 (last accessed 02.02.16).

      ].
      The UK Prospective Diabetes Study (UKPDS) revealed that intensive diabetes management from diagnosis was associated with a reduced risk of microvascular complications by the end of the 10-year trial period [
      • UKPDS Study Group
      Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).
      ], and a reduced risk of myocardial infarction and all-cause death reported in the decade following [
      • Holman R.R.
      • Paul S.K.
      • Bethel A.
      • et al.
      10-year follow-up of intensive glucose control in type 2 diabetes.
      ]. Subsequent shorter-term landmark trials that recruited patients at high risk of cardiovascular disease (CVD) with a long duration of diabetes, and that involved stringent glycaemic targets and more complex treatment regimens in the intensive arm, did not show such clear-cut benefits in terms of macrovascular complications and mortality [
      • Ray K.K.
      • Seshasai S.R.
      • Wijesuriva S.
      • et al.
      Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials.
      ]. All the trials demonstrated a reduced risk of microvascular complications (some more substantial than others) but only UKPDS demonstrated a reduced risk of macrovascular disease and mortality at the end-of-trial (reaching significance in the 10-year follow-up) [
      • Holman R.R.
      • Paul S.K.
      • Bethel A.
      • et al.
      10-year follow-up of intensive glucose control in type 2 diabetes.
      ]. Follow-up of the Veterans Affairs Diabetes Trial (VADT) for almost 10 years revealed a reduced risk of cardiovascular event but not all-cause mortality in participants from the intensive treatment arm [
      • Hayward R.A.
      • Reaven P.D.
      • Wiitala W.L.
      • et al.
      Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes.
      ]. Results from these trials demonstrate the importance of individualising treatment targets (according to established vascular complications and comorbidities [
      • Inzucchi S.E.
      • Bergenstal R.M.
      • Buse J.B.
      • et al.
      Management of hyperglycemia in type 2 diabetes: 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes.
      ]) and suggest that delayed treatment intensification can allow irreversible diabetes-related complications to develop. The latest results from a retrospective cohort study confirm this, since a 1-year delay in treatment intensification in uncontrolled patients significantly increased the risk of myocardial infarction, heart failure, stroke and a composite endpoint of cardiovascular events (Fig. 1) [
      • Paul S.K.
      • Klein K.
      • Thorsted B.L.
      • et al.
      Delay in treatment intensification increases the risks of cardiovascular events in patients with type 2 diabetes.
      ].
      Fig. 1
      Fig. 1Consequences of delayed intervention in patients without previous CVD.
      The risk of CVD is shown for patients with HbA1c consistently above 53 mmol/mol (7%) in the 2 years following diagnosis for whom treatment intensification is delayed by at least 1 year versus that of patients with HbA1c consistently below 53 mmol/mol (7%) in the same period
      [
      • Paul S.K.
      • Klein K.
      • Thorsted B.L.
      • et al.
      Delay in treatment intensification increases the risks of cardiovascular events in patients with type 2 diabetes.
      ]
      .
      CI, confidence interval; CVD, cardiovascular disease; CVE, cardiovascular event; HbA1c, glycated haemoglobin; HF, heart failure; IT, intensification of treatment; MI, myocardial infarction.
      Illustration based on data from Paul et al.
      [
      • Paul S.K.
      • Klein K.
      • Thorsted B.L.
      • et al.
      Delay in treatment intensification increases the risks of cardiovascular events in patients with type 2 diabetes.
      ]
      . This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
      The current guidelines recommend stepwise intensification [
      • Inzucchi S.E.
      • Bergenstal R.M.
      • Buse J.B.
      • et al.
      Management of hyperglycemia in type 2 diabetes: 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes.
      ,

      NICE guideline (December 2015), Type 2 Diabetes in Adults: Management (NG28). Available at: https://www.nice.org.uk/guidance/ng28/resources/type-2-diabetes-in-adults-management-1837338615493 (last accessed 02.02.16).

      ], and while resistance to intensification is evident at every step, it appears to be more pronounced when considering initiating insulin [
      • Khunti K.
      • Wolden M.L.
      • Thorsted B.L.
      • et al.
      Clinical inertia in people with type 2 diabetes: a retrospective cohort study of more than 80,000 people.
      ], despite this being the most effective agent for lowering blood glucose when used appropriately [
      • Inzucchi S.E.
      • Bergenstal R.M.
      • Buse J.B.
      • et al.
      Management of hyperglycemia in type 2 diabetes: 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes.
      ]. Furthermore, few patients intensify their insulin regimen appropriately [
      • Blak B.T.
      • Smith H.T.
      • Hards M.
      • et al.
      A retrospective database study of insulin initiation in patients with type 2 diabetes in UK primary care.
      ,
      • Khunti K.
      • Damci T.
      • Meneghini L.
      • et al.
      SOLVE study group. Study of Once Daily Levemir (SOLVE™): insights into the timing of insulin initiation in people with poorly controlled type 2 diabetes in routine clinical practice.
      ]. The failure to close the gap between best practice and the patient’s usual level of care is termed ‘clinical inertia’ [
      • Phillips L.S.
      • Branch W.T.
      • Cook C.B.
      • et al.
      Clinical inertia.
      ].
      The majority of clinical inertia studies are focused on the US, the UK and Canada. In the present study, we review the evidence for clinical inertia in the UK, where healthcare is free for all, and also the barriers and potential solutions.

      2. Methods

      A focused literature search for studies on clinical inertia relating to insulin initiation and intensification in patients with type 2 diabetes in the UK was conducted using PubMed, Scopus and Google Scholar. Search terms included ‘type 2 diabetes’, ‘insulin intensification’, ‘delay’, ‘time’, ‘inertia’, ‘insulin avoidance’, ‘escalation’ and ‘reluctance’. Only studies conducted in the UK were included. Table 1 illustrates some of the key studies [
      • Khunti K.
      • Wolden M.L.
      • Thorsted B.L.
      • et al.
      Clinical inertia in people with type 2 diabetes: a retrospective cohort study of more than 80,000 people.
      ,
      • Blak B.T.
      • Smith H.T.
      • Hards M.
      • et al.
      A retrospective database study of insulin initiation in patients with type 2 diabetes in UK primary care.
      ,
      • Khunti K.
      • Vora J.
      • Davies M.
      Results from the UK cohort of SOLVE: providing insights into the timing of insulin initiation in people with poorly controlled type 2 diabetes in routine clinical practice.
      ,
      • Mata-Cases M.
      • Benito-Badorrey B.
      • Roura-Olmeda P.
      • et al.
      Clinical inertia in the treatment of hyperglycemia in type 2 diabetes patients in primary care.
      ,
      • Evans M.L.
      • Sharplin P.
      • Owens D.R.
      • et al.
      Insulin usage in type 2 diabetes mellitus patients in UK clinical practice: a retrospective cohort-based analysis using the THIN database.
      ,
      • Calvert M.J.
      • McManus R.J.
      • Freemantle N.
      Management of type 2 diabetes with multiple oral hypoglycaemic agents or insulin in primary care: retrospective cohort study.
      ,
      • Zografou I.
      • Strachan M.W.J.
      • McKnight J.
      Delay in starting insulin after failure of other treatments in patients with type 2 diabetes mellitus.
      ,
      • Khunti K.
      • Nikolajsen A.
      • Thorsted B.L.
      • et al.
      Clinical inertia with regard to intensifying therapy in people with type 2 diabetes treated with basal insulin.
      ].
      Table 1Studies reporting clinical inertia for insulin therapy in the UK.
      StudyNumber of patientsKey findings
      Khunti et al.
      • Khunti K.
      • Vora J.
      • Davies M.
      Results from the UK cohort of SOLVE: providing insights into the timing of insulin initiation in people with poorly controlled type 2 diabetes in routine clinical practice.
      UK cohort of SOLVE (n = 761)At the time of insulin initiation, the UK cohort had a higher baseline HbA1c compared with the global population of SOLVE (84 mmol/mol [9.8%] vs. 74 mmol/mol [8.9%], respectively), despite a shorter duration of disease
      Mata-Cases et al.
      • Mata-Cases M.
      • Benito-Badorrey B.
      • Roura-Olmeda P.
      • et al.
      Clinical inertia in the treatment of hyperglycemia in type 2 diabetes patients in primary care.
      2783Of 997 not achieving glycaemic targets, only 66.8% intensified, with an even smaller proportion of them initiating insulin treatment (3.7%). Mean HbA1c values in patients for whom treatment intensified vs non-intensified were 68 mmol/mol (8.4%) vs. 66 mmol/mol (8.2%), p < 0.05.
      Khunti et al.
      • Khunti K.
      • Wolden M.L.
      • Thorsted B.L.
      • et al.
      Clinical inertia in people with type 2 diabetes: a retrospective cohort study of more than 80,000 people.
      81,573Retrospective cohort study on patients with type 2 diabetes in Clinical Practice Research Datalink looked at time to treatment intensification in those receiving one, two or three OADs. Mean HbA1c at intensification with an OAD or insulin for people taking one, two or three OADs was 72 mmol/mol (8.7%), 76 mmol/mol (9.1%) and 83 mmol/mol (9.7%). Median time to intensification with insulin was >7.1, >6.1 or 6.0 years, respectively.
      Evans et al.
      • Evans M.L.
      • Sharplin P.
      • Owens D.R.
      • et al.
      Insulin usage in type 2 diabetes mellitus patients in UK clinical practice: a retrospective cohort-based analysis using the THIN database.
      128,568Retrospective cohort-based study revealed that mean HbA1c at insulin initiation was 80 mmol/mol (9.5%) (one OAD), 81 mmol/mol (9.6%) (two), 83 mmol/mol (9.7%) (three) and 87 mmol/mol (10.1%) (four), with insulin initiated only after there had been an average increase in HbA1c of 8 mmol/mol (0.7%).
      Calvert et al.
      • Calvert M.J.
      • McManus R.J.
      • Freemantle N.
      Management of type 2 diabetes with multiple oral hypoglycaemic agents or insulin in primary care: retrospective cohort study.
      14,824 people on DIN-LINK database includedStudy examined the extent of monitoring and glycaemic control in patients with type 2 diabetes prescribed oral agents and/or insulin, and investigated transition to insulin. Only 34% had HbA1c assessments 6 months before and after initiation of their last oral therapy. Of the patients with HbA1c assessments, 62% had evidence of poor glycaemic control following therapy. Median time to insulin for patients prescribed multiple oral agents was 7.7 years.
      Zografou et al.
      • Zografou I.
      • Strachan M.W.J.
      • McKnight J.
      Delay in starting insulin after failure of other treatments in patients with type 2 diabetes mellitus.
      509Retrospective study examining patients who initiated insulin therapy between 2002 and 2011 from the Scottish Care Information-Diabetes Collaboration (SCI-DC) database (Scotland). Patients spent a median period of 49 (0–325) months with HbA1c > 53 mmol/mol (>7%), 25 (0–163) months with HbA1c >64 mmol/mol (>8%) and 10 (0–135) months with HbA1c >75 mmol/mol (>9%), and concluded that healthcare professionals delay the initiation of insulin in patients with type 2 diabetes until their HbA1c exceeds 86 mmol/mol (10%). As a result, patients are exposed to a significant glycaemic burden.
      Blak et al.
      • Blak B.T.
      • Smith H.T.
      • Hards M.
      • et al.
      A retrospective database study of insulin initiation in patients with type 2 diabetes in UK primary care.
      4045Retrospective cohort study on patients in The Health Improvement Network (THIN) database who initiated insulin for the first time between 2004 and 2006. Of 3815 patients followed up, the initial insulin regimen remained unchanged for 75.1%, while 13.7% discontinued, 7% switched and only 4.7% intensified, despite only 17.3% of patients achieving glycaemic target <53 mmol/mol (7%).
      Khunti et al.
      • Khunti K.
      • Nikolajsen A.
      • Thorsted B.L.
      • et al.
      Clinical inertia with regard to intensifying therapy in people with type 2 diabetes treated with basal insulin.
      11,69631% of patients in the UK Clinical Practice Research Datalink database receiving basal insulin therapy between 2004 and 2011 who were clinically eligible for treatment intensification were treated accordingly. Of the 37% of patients who did have treatment regimens intensified, 50%, 43% and 7% were intensified with bolus insulin, premix insulin or GLP-1RAs, respectively. The median time to intensification was 4.3 years [4.1; 4.6]95%CI from basal insulin initiation in all patients and 3.7 years [3.4; 4.0]95%CI from the time HbA1c ≥ 7.5% was recorded.
      CI, confidence interval; GLP-1RA, glucagon-like peptide-1 receptor agonist; HbA1c, glycated haemoglobin; OAD, oral antidiabetic drug.

      3. What evidence is there of clinical inertia?

      Studies show that insulin initiation is delayed until after multiple oral antidiabetic drug (OAD) failures and deterioration of glycaemic control well beyond recommended guidelines [
      • Khunti S.
      • Davies M.J.
      • Khunti K.
      Clinical inertia in the management of type 2 diabetes mellitus: a focused literature review.
      ]. Clinical inertia is not restricted to the UK, as demonstrated by results of the Study of Once Daily Levemir (SOLVE™; Table 1) [
      • Khunti K.
      • Damci T.
      • Meneghini L.
      • et al.
      SOLVE study group. Study of Once Daily Levemir (SOLVE™): insights into the timing of insulin initiation in people with poorly controlled type 2 diabetes in routine clinical practice.
      ,
      • Khunti K.
      • Vora J.
      • Davies M.
      Results from the UK cohort of SOLVE: providing insights into the timing of insulin initiation in people with poorly controlled type 2 diabetes in routine clinical practice.
      ]. Reasons why blood glucose levels were higher in the UK at the time of insulin initiation were not reported.
      Relatively few studies examine clinical inertia with insulin intensification, but results show similar delays (Table 1). A retrospective analysis of data from insulin-treated patients with type 2 diabetes within The Health Improvement Network (THIN) UK primary care database demonstrated that intensification was associated with high HbA1c (mean 77 mmol/mol [9.2%] before change) and longer duration of diabetes, whereas lack of intensification was associated with an increased risk of co-morbidities. The proportion of patients who intensified basal insulin or switched to prandial/premixed insulin had a mean HbA1c of 71 mmol/mol (8.6%) and 69 mmol/mol (8.5%) following change in therapy, respectively. This is in contrast to the mean HbA1c values that were achieved by participants of phase 3 clinical trials investigating these prandial or premix insulin analogues [
      • Blak B.T.
      • Smith H.T.
      • Hards M.
      • et al.
      A retrospective database study of insulin initiation in patients with type 2 diabetes in UK primary care.
      ].
      A retrospective cohort study of 11,696 insulin-treated UK patients revealed that 31% of patients who were clinically eligible for intensification (HbA1c of 58 mmol/mol [≥7.5%]) were treated accordingly (Table 1) [
      • Khunti K.
      • Nikolajsen A.
      • Thorsted B.L.
      • et al.
      Clinical inertia with regard to intensifying therapy in people with type 2 diabetes treated with basal insulin.
      ]. Older age, longer duration of diabetes and higher Charlson comorbidity index were all associated with a longer time to intensification, which might be expected given that less stringent HbA1c targets are recommended for these populations [
      • Inzucchi S.E.
      • Bergenstal R.M.
      • Buse J.B.
      • et al.
      Management of hyperglycemia in type 2 diabetes: 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes.
      ,

      NICE guideline (December 2015), Type 2 Diabetes in Adults: Management (NG28). Available at: https://www.nice.org.uk/guidance/ng28/resources/type-2-diabetes-in-adults-management-1837338615493 (last accessed 02.02.16).

      ]. However, only a small reduction in time to intensification was observed when applying a less stringent HbA1c cut-off of ≥64 mmol/mol (8.0%) to the same entire study population. Use of OADs also had a significant association with time to intensification, correlating with a longer delay; yet receiving ≥2 OADs was associated with a reduced delay versus receiving one OAD [
      • Khunti K.
      • Nikolajsen A.
      • Thorsted B.L.
      • et al.
      Clinical inertia with regard to intensifying therapy in people with type 2 diabetes treated with basal insulin.
      ].
      Results from a multinational survey, ‘Management Of Diabetes In Future Years’ (MODIFY), revealed that 30% of primary care physicians overall never/rarely personally intensified insulin (compared with 4% of specialists), despite 92% of physicians agreeing with the statement “insulin intensification is an essential element of diabetes management”. However, it is not known whether any of these primary care physicians were lacking the necessary resources for insulin intensification and so referred patients to a specialist [
      • Shah B.R.
      • Hux J.E.
      • Laupacis A.
      • et al.
      Clinical inertia in response to inadequate glycemic control: do specialists differ from primary care physicians.
      ]. A total of 95% of physicians cited “excessive levels of HbA1c” as a key indicator to consider intensification, but it was not reported to what extent the time their patients spent uncontrolled contributed to their decision [
      • Cuddihy R.M.
      • Philis-Tsimikas A.
      • Nazeri A.
      Type 2 diabetes care and insulin intensification: is a more multidisciplinary approach needed? Results from the MODIFY survey.
      ].
      To summarise, these studies demonstrate that current guidelines are largely not being adhered to.

      4. Do the current guidelines help?

      The proportion of people with diabetes uncontrolled on their current therapy seems at odds with the wide range of effective antidiabetic therapies now available. However, the challenge is to consolidate the plethora of clinical trial and real-world data into a clear set of guidelines on how to manage diabetes both effectively and economically.
      The key points of the joint American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) statement [
      • Inzucchi S.E.
      • Bergenstal R.M.
      • Buse J.B.
      • et al.
      Management of hyperglycemia in type 2 diabetes: 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes.
      ] and the National Institute for Health and Care Excellence (NICE) guidelines [

      NICE guideline (December 2015), Type 2 Diabetes in Adults: Management (NG28). Available at: https://www.nice.org.uk/guidance/ng28/resources/type-2-diabetes-in-adults-management-1837338615493 (last accessed 02.02.16).

      ] regarding timely achievement of glycaemic control in type 2 diabetes are summarised in Table 2.
      Table 2A comparison of the current guidelines for type 2 diabetes
      • Inzucchi S.E.
      • Bergenstal R.M.
      • Buse J.B.
      • et al.
      Management of hyperglycemia in type 2 diabetes: 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes.
      ,

      NICE guideline (December 2015), Type 2 Diabetes in Adults: Management (NG28). Available at: https://www.nice.org.uk/guidance/ng28/resources/type-2-diabetes-in-adults-management-1837338615493 (last accessed 02.02.16).

      .
      EASD/ADANICE
      TargetsRecommends lowering HbA1c to <53 mmol/mol (<7%) in most patients to reduce the incidence of microvascular disease. More stringent HbA1c targets (e.g. 42–48 mmol/mol [6–6.5%]) might be considered in selected patients (short disease duration, long life expectancy, no significant CVD) if this can be achieved without significant hypoglycaemia or other adverse events. Conversely, less stringent HbA1c goals (e.g. 58–64+ mmol/mol [7.5–8%+]) are appropriate for patients with a history of severe hypoglycaemia, limited life expectancy, advanced complications, extensive comorbid conditions and those in whom the target is difficult to obtain despite “best efforts according to guidelines”Set a target HbA1c level of 48 mmol/mol (6.5%) for most adults with type 2 diabetes that is managed either by lifestyle and diet, or by lifestyle and diet in combination with a single drug that is not associated with hypoglycaemia. For adults receiving a drug associated with hypoglycaemia, aim to achieve HbA1c of 53 mmol/mol (7.0%). If HbA1c levels are not adequately controlled by a single drug and rise to ≥58 mmol/mol (7.5%), intensify drug treatment, set a target HbA1c of 53 mmol/mol (7.0%) and reinforce advice about diet, lifestyle and adherence to drug treatment. Consider less stringent HbA1c targets (∼53–58 mmol/mol [7.0–7.5%]) in appropriate cases, similar to those outlined in ADA/EASD statement
      • Inzucchi S.E.
      • Bergenstal R.M.
      • Buse J.B.
      • et al.
      Management of hyperglycemia in type 2 diabetes: 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes.
      .
      TreatmentWhile encouraging therapeutic lifestyle change is important at diagnosis, periodic counselling should also be integrated into the treatment programme. Insulin is a possible first intensification step of metformin in the two-drug combination tier depending on patient- and disease-specific factors present. Addition of a third drug, namely TZD, DPP-4i, SGLT2i or GLP-1RA, is then recommended if the patient remains uncontrolled. Similarly, addition of insulin to those uncontrolled on metformin + GLP-1RA is another recommendation. More complex insulin strategies are ultimately recommended if the combinations above failSensible recommendations regarding lifestyle, patient education, monitoring and targets. Insulin recommended as the second intensification of drug treatment only. GLP-1RAs are only recommended in patients if triple therapy with metformin and two other oral drugs is not effective, not tolerated or contraindicated, and who either would benefit from weight loss or for whom insulin therapy would have a significant occupational impact. Lacking clear information regarding intensification of insulin, particularly with OADs. A limited number of insulin intensification strategies are included in the NICE algorithm: switching to pre-mix insulins; or intensification with a GLP-1RA (with specialist support) or an SGLT2i.
      TimelinesIf HbA1c target not achieved after ∼3 months of therapy, add additional therapyLacking explicit guidelines, with the exception of stopping rules for GLP-1RA and pioglitazone. Recommends testing HbA1c levels every 3–6 months until stable on unchanged therapy, and every 6 months thereafter.
      CVD, cardiovascular disease; DPP-4i, dipeptidyl peptidase-4 inhibitor; GLP-1RA, glucagon-like peptide-1 receptor agonist; HbA1c, glycated haemoglobin; SGLT2i, sodium-glucose co-transporter-2 inhibitor; TZD, thiazolidinedione.
      The NICE guidelines [

      NICE guideline (December 2015), Type 2 Diabetes in Adults: Management (NG28). Available at: https://www.nice.org.uk/guidance/ng28/resources/type-2-diabetes-in-adults-management-1837338615493 (last accessed 02.02.16).

      ] advise treatment escalation when HbA1c rises to >58 mmol/mol (>7.5%) until control is achieved, implying that clinicians should be content with HbA1c of between 48 and 58 mmol/mol (6.5–7.5%) even in patients for whom 48 mmol/mol (6.5%) would be a suitable target. Little information is offered regarding the time a patient should spend at hyperglycaemia before treatment intensification. This propagates a reactive approach wherein clinicians wait for the worsening of hyperglycaemia or complications to arise before intensifying treatment, and patients will likely reach glycaemic targets for only short periods, if at all (Fig. 2) [
      • Del Prato S.
      • Felton A.-M.
      • Munro N.
      • et al.
      Global Partnership For Effective Diabetes Management. Improving glucose management: ten steps to get more patients with type 2 diabetes to glycaemic goal.
      ].
      Fig. 2
      Fig. 2Median time to intensification and mean HbA1c at intensification in patients with type 2 diabetes currently treated with one or two OADs with intensification to two OADs or insulin, respectively.
      OAD, oral antidiabetic drug.
      Republished with permission of Medinews (Cardiology) News Ltd, from Campbell IW, Br J Cardiol 2000;7:625–31; permission conveyed through Copyright Clearance Center, Inc. Adapted with permission from Del Prato et al.
      [
      • Del Prato S.
      • Felton A.-M.
      • Munro N.
      • et al.
      Global Partnership For Effective Diabetes Management. Improving glucose management: ten steps to get more patients with type 2 diabetes to glycaemic goal.
      ]
      , with data from Khunti et al.
      [
      • Khunti K.
      • Wolden M.L.
      • Thorsted B.L.
      • et al.
      Clinical inertia in people with type 2 diabetes: a retrospective cohort study of more than 80,000 people.
      ]
      .
      The joint statement update issued from ADA/EASD [
      • Inzucchi S.E.
      • Bergenstal R.M.
      • Buse J.B.
      • et al.
      Management of hyperglycemia in type 2 diabetes: 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes.
      ], however, does provide clear timelines of up to 3 months for escalation.
      The detrimental effect that variation between the ADA/EASD and NICE guidelines could have on clinician adherence to guidelines has been discussed elsewhere [
      • O’Hare J.P.
      • Millar-Jones D.
      • Hanif W.
      • et al.
      The new NICE guidelines for type 2 diabetes—a critical analysis.
      ]. Between 2000 and 2007, the mean HbA1c of insulin users with type 2 diabetes in the UK reduced by only 1 mmol/mol (0.1%) from 69 mmol/mol (8.5%) to 68 mmol/mol (8.4%), despite – and in contrast to – the NICE and ADA/EASD guidelines introduced during this period [
      • Currie C.J.
      • Gale E.A.
      • Poole C.D.
      Estimation of primary care treatment costs and treatment efficacy for people with type 1 and type 2 diabetes in the United Kingdom from 1997 to 2007.
      ].
      The guidelines also have a number of drawbacks in common, an unavoidable one being that they quickly become out of date because of the constantly changing landscape of diabetes treatment. In addition, both guidelines recommend stepwise addition of therapy according to HbA1c levels. This approach often fails to correct the underlying pathophysiological defects of type 2 diabetes [
      • DeFronzo R.A.
      • Eldor R.
      • Abdul-Ghani M.
      Pathophysiologic approach to therapy in patients with newly diagnosed type 2 diabetes.
      ]. While the therapeutic benefit of a medication must be balanced against its financial cost, the focus on cost-effectiveness by NICE has been criticised as short-sighted in view of the risk of diabetic complications later in life [
      • Wilding J.P.
      • Rajeev S.P.
      • DeFronzo R.A.
      Positioning SGLT2 inhibitors/incretin-based therapies in the treatment algorithm.
      ]. Therefore, the task of tackling clinical inertia should be kept in mind when updating the guidelines.
      While there is certainly room for improvement in the guidelines, particularly those from NICE, the evidence suggests that clinical inertia in the UK is also caused by a lack of adherence to any of the available guidelines.

      5. Why is there clinical inertia?

      5.1 Clinician-level barriers

      Barriers to treatment intensification can be divided into those at the patient, clinician or system level, and the majority of these barriers were discussed in a set of interviews conducted for a UK-based qualitative study [
      • Zafar A.
      • Stone M.A.
      • Davies M.J.
      • Khunti K.
      Acknowledging and allocating responsibility for clinical inertia in the management of type 2 diabetes in primary care: a qualitative study.
      ].
      A major clinician-level hurdle is a limited awareness of clinical inertia, resulting in overestimation by clinicians of their quality of care and adherence to guidelines [
      • Phillips L.S.
      • Branch W.T.
      • Cook C.B.
      • et al.
      Clinical inertia.
      ,
      • Khunti S.
      • Davies M.J.
      • Khunti K.
      Clinical inertia in the management of type 2 diabetes mellitus: a focused literature review.
      ]. This issue may be exacerbated as the management of chronic diseases increasingly becomes a primary care responsibility because insulin therapy requires specialist training and more patient-contact time than OAD therapy.
      Development of vascular complications increases the patient’s risk of mortality and it is therefore important to address increases in HbA1c and risk factors for CVD, as demonstrated by the Steno-2 study [
      • Gæde P.
      • Lund-Andersen H.
      • Parving H.H.
      • Pedersen O.
      Effect of a multifactorial intervention mortality in type 2 diabetes.
      ]. However, GPs may not be familiar with the current opinion that aggressive control early on following diagnosis leads to significant benefit in appropriate patients [
      • Zafar A.
      • Stone M.A.
      • Davies M.J.
      • Khunti K.
      Acknowledging and allocating responsibility for clinical inertia in the management of type 2 diabetes in primary care: a qualitative study.
      ]. As a result, the precious time GPs do have is often focused on their patients’ current HbA1c and cholesterol levels, as well as their blood pressure and meeting Quality Outcomes Framework targets, rather than the glycaemic burden caused by the duration of poor glucose control [
      • Zografou I.
      • Strachan M.W.J.
      • McKnight J.
      Delay in starting insulin after failure of other treatments in patients with type 2 diabetes mellitus.
      ].
      Patients with multimorbidity are common and pose a major challenge [
      • Guthrie B.
      • Payne K.
      • Alderson P.
      • et al.
      Adapting clinical guidelines to take account of multimorbidity.
      ], with respect to balancing the benefit of lowering blood glucose against the risk of adverse side effects in these patients. Following results from VADT, ADVANCE and ACCORD, and as documented in a key study by Currie et al. [
      • Currie C.J.
      • Poole C.D.
      • Evans M.
      • et al.
      Mortality and other important diabetes-related outcomes with insulin vs other antihyperglycemic therapies in type 2 diabetes.
      ], the fear of adverse side effects impacts the decisions made by patients and clinicians. In a global survey of 1250 physicians, including 150 from the UK, 75.5% reported that they would intensify treatment more readily if it were not for concerns about hypoglycaemia [
      • Peyrot M.
      • Barnett A.H.
      • Meneghini L.F.
      • Schumm-Draeger P.M.
      Insulin adherence behaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study.
      ].
      Other clinician-level barriers stem from their concerns over patient adherence, perceiving their patients as unable or unwilling to adapt to the increasingly complex regimen. Results from a questionnaire revealed that fear of injection pain was a low-ranking factor for patients considering insulin therapy, whereas family physicians perceived this to be a major patient concern [
      • Nakar S.
      • Yitzhaki G.
      • Rosenberg R.
      • Vinker S.
      Transition to insulin in type 2 diabetes: family physicians’ misconception of patients’ fears contributes to existing barriers.
      ]. The belief that patients will refuse to initiate/intensify insulin therapy is a major cause of psychological insulin resistance [
      • Phillips P.
      Type 2 diabetes—failure: blame and guilt in the adoption of insulin therapy.
      ], and the results from this questionnaire suggest it might be untrue.
      These barriers are exacerbated by the lack of time available to GPs to adequately tackle concerns.

      5.2 Patient-level barriers

      There are several misperceptions about insulin therapy (reviewed in Polonsky et al. [
      • Polonsky W.H.
      • Jackson R.A.
      What’s so tough about taking insulin? Addressing the problem of psychological insulin resistance in type 2 diabetes.
      ]) that are more frequently contributory factors for insulin-naïve versus insulin-experienced patients [
      • Kunt T.
      • Snoek F.J.
      Barriers to insulin initiation and intensification and how to overcome them.
      ], suggesting that further education on these issues would resolve them [
      • Zafar A.
      • Stone M.A.
      • Davies M.J.
      • Khunti K.
      Acknowledging and allocating responsibility for clinical inertia in the management of type 2 diabetes in primary care: a qualitative study.
      ]. Problematic patient beliefs include the belief that insulin therapy is not efficacious [
      • Peyrot M.
      • Rubin R.R.
      • Lauritzen T.
      • International DAWN Advisory Panel
      • et al.
      Resistance to insulin therapy among patients and providers: results of the cross-national diabetes attitudes, wishes, and needs study.
      ], that their quality of life will drop considerably [
      • Kunt T.
      • Snoek F.J.
      Barriers to insulin initiation and intensification and how to overcome them.
      ,
      • Peyrot M.
      • Rubin R.R.
      • Lauritzen T.
      • International DAWN Advisory Panel
      • et al.
      Resistance to insulin therapy among patients and providers: results of the cross-national diabetes attitudes, wishes, and needs study.
      ], and that they will not be able to adhere to increasingly complex regimens [
      • Peyrot M.
      • Rubin R.R.
      • Lauritzen T.
      • International DAWN Advisory Panel
      • et al.
      Resistance to insulin therapy among patients and providers: results of the cross-national diabetes attitudes, wishes, and needs study.
      ]. Patient fear of unwanted side effects such as weight gain and hypoglycaemia [
      • Peyrot M.
      • Barnett A.H.
      • Meneghini L.F.
      • Schumm-Draeger P.M.
      Insulin adherence behaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study.
      ,
      • Polonsky W.H.
      • Jackson R.A.
      What’s so tough about taking insulin? Addressing the problem of psychological insulin resistance in type 2 diabetes.
      ,
      • Kunt T.
      • Snoek F.J.
      Barriers to insulin initiation and intensification and how to overcome them.
      ], and of injection pain [
      • Vijan S.
      • Hayward R.A.
      • Ronis D.L.
      • Hofer T.P.
      Brief report. The burden of diabetes therapy: implications for the design of effective patient-centered treatment regimens.
      ], can also delay intensification. Insulin-experienced patients, unsurprisingly, do not view insulin regimens to be as highly burdensome as do insulin-naïve patients, until multiple injections are involved [
      • Vijan S.
      • Hayward R.A.
      • Ronis D.L.
      • Hofer T.P.
      Brief report. The burden of diabetes therapy: implications for the design of effective patient-centered treatment regimens.
      ].
      In a systematic review of factors affecting adherence to insulin therapy [
      • Davies M.J.
      • Gagliardino J.J.
      • Gray L.J.
      • et al.
      Real-world factors affecting adherence to insulin therapy in patients with type 1 or type 2 diabetes mellitus: a systematic review.
      ], positive predictors of insulin adherence included diabetic nurse specialist support; switching to a pen device; hypoglycaemia awareness; experience of liaison psychiatry or cognitive behavioural therapy; and lower perceived consequences of diabetes/higher perception of personal control. Negative predictors included a large number of injections, female gender and lower HbA1c. However, few of these predictors were consistently reported across studies included in the systematic review.
      Self-reported rates of adherence also varied across these studies from 43–86% [
      • Davies M.J.
      • Gagliardino J.J.
      • Gray L.J.
      • et al.
      Real-world factors affecting adherence to insulin therapy in patients with type 1 or type 2 diabetes mellitus: a systematic review.
      ]. Another study revealed that one-third of patients reported insulin omission on at least one day in the last month, while three-quarters of physicians reported that their patients did not take insulin as prescribed [
      • Peyrot M.
      • Barnett A.H.
      • Meneghini L.F.
      • Schumm-Draeger P.M.
      Insulin adherence behaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study.
      ]. These discrepancies highlight the problem with objective assessment of adherence (i.e. it is difficult to define and is perceived differently according to the questions posed and background knowledge).
      A more objective, although arguably less informative, output is the proportion of patients who discontinue insulin therapy. Among 6072 insulin-treated patients in the UK Clinical Practice Research Datalink database, 32.1% stopped basal insulin therapy. Reasons for stopping were unknown [
      • Khunti K.
      • Nikolajsen A.
      • Thorsted B.L.
      • et al.
      Clinical inertia with regard to intensifying therapy in people with type 2 diabetes treated with basal insulin.
      ]. Pscherer et al. [
      • Pscherer S.
      • Chou E.
      • Dippel F.-W.
      • et al.
      Treatment persistence after initiating basal insulin in type 2 diabetes patients: a primary care database analysis.
      ] compared persistence after 2 years with treatment regimens involving insulin glargine, insulin detemir or neutral protamine Hagedorn insulin in combination with either a prandial insulin or an OAD. In basal–oral therapy regimens, 2-year persistence varied from 53% to 65%, whereas in intensified conventional therapy, persistence was around 85%. Reasons for discontinuation are unknown, but predictors for discontinuation included type of insulin, diabetic co-medication and patient characteristics (diagnosed heart failure). In a small US study (N = 1563 patients uncontrolled on insulin), 97 patients discontinued insulin therapy and 157 did not initiate therapy [
      • Oliveria S.A.
      • Menditto L.A.
      • Yood M.U.
      • et al.
      Barriers to the initiation of, and persistence with, insulin therapy.
      ]. The most common reason for discontinuation was injection-related concerns (74%), with 47.1% of ‘discontinuers’ and 86.1% of ‘non-initiators’ doing so on a healthcare professional’s (HCP’s) advice. Further details regarding the HCPs’ reasons were not available but this highlights how patient and clinician barriers overlap [
      • Oliveria S.A.
      • Menditto L.A.
      • Yood M.U.
      • et al.
      Barriers to the initiation of, and persistence with, insulin therapy.
      ].

      6. What can we do to overcome clinical inertia?

      6.1 Tackling clinician barriers

      The shift of responsibility from secondary care to primary care in the UK necessitates extra resources for GPs. This may be in the form of formal education, assistance from nurses and informed feedback. In the US, non-insulin-treated patients with hypertension and type 2 diabetes (N = 157) benefited from a significant improvement in mean HbA1c (−8 mmol/mol [−0.7%], p = 0.02) and high-density lipoprotein cholesterol (+2.6 mg/dL, p = 0.02) when a new disease management programme was implemented by a nurse practitioner and physician duo, versus usual care by a physician [
      • Litaker D.
      • Mion L.
      • Planavsky L.
      • et al.
      Physician–nurse practitioner teams in chronic disease management: the impact on costs, clinical effectiveness, and patients' perception of care.
      ]. These findings are supported by several other studies that describe more timely treatment intensification when GPs are assisted by nurses [
      • Khunti S.
      • Davies M.J.
      • Khunti K.
      Clinical inertia in the management of type 2 diabetes mellitus: a focused literature review.
      ].
      Perhaps a simpler avenue proposed for tackling clinician barriers is setting up channels of computer-based direction and/or specialist feedback to assist GPs [
      • Zafar A.
      • Davies M.
      • Azhar A.
      • Khunti K.
      Clinical inertia in management of T2DM.
      ]. For example, significantly more clinicians who were supported with an automated decision support tool and/or an educational DVD in a randomised controlled trial (RCT) correctly identified a glycaemic anomaly and proceeded with the appropriate treatment regimen [
      • Rodbard H.W.
      • Schnell O.
      • Unger J.
      • et al.
      Use of an automated decision support tool optimizes clinicians’ ability to interpret and appropriately respond to structured self-monitoring of blood glucose data.
      ].
      Other methods to support GPs have included case management with a practice nurse or pharmacist directing treatment decisions according to an approved, detailed treatment algorithm under the supervision of a physician, and automated appointment reminders for patients [
      • Zafar A.
      • Davies M.
      • Azhar A.
      • Khunti K.
      Clinical inertia in management of T2DM.
      ].

      6.2 Tackling patient-level barriers

      Rectifying the issue of inadequate patient education and impaired communication between the patient and HCP involves a great deal of time [
      • Khunti S.
      • Davies M.J.
      • Khunti K.
      Clinical inertia in the management of type 2 diabetes mellitus: a focused literature review.
      ]. Therefore, time-saving educational strategies such as self-management programmes that empower and equip the patient to manage their blood glucose have been investigated. Promising results were reported in a systematic review with meta-analyses that evaluated the effect of group-based diabetes self-management education (DSME) [
      • Steinsbekk A.
      • Rygg L.Ø.
      • Lisulo M.
      • et al.
      Group based diabetes self-management education compared to routine treatment for people with type 2 diabetes mellitus. A systematic review with meta-analysis.
      ]. This systematic review revealed that DSME was associated with a significant reduction in HbA1c at 6 months (0.44% points; p = 0.0006, 13 studies, 1883 participants), and this reduction was maintained at 2 years (0.87% points; p < 0.00001, 3 studies, 397 participants) according to RCTs conducted up to January 2008 [
      • Steinsbekk A.
      • Rygg L.Ø.
      • Lisulo M.
      • et al.
      Group based diabetes self-management education compared to routine treatment for people with type 2 diabetes mellitus. A systematic review with meta-analysis.
      ].
      Clinical trials have demonstrated significantly greater reductions in HbA1c versus that of usual care when a Diabetes Education and Self-Management for Ongoing and Newly Diagnosed (DESMOND) model of education was coupled with an intensive treatment regimen in patients referred from UK general practices and specialist clinics [
      • Crasto W.
      • Jarvis J.
      • Khunti K.
      • et al.
      Multifactorial intervention in individuals with type 2 diabetes and microalbuminuria: the Microalbuminuria Education and Medication Optimisation (MEMO) study.
      ]. In patients with type 2 diabetes and microalbuminuria, randomisation to intensive intervention with a structured DESMOND model of patient education yielded significant improvements in HbA1c, blood pressure and cholesterol versus that of usual care. Importantly, this tight control was achieved with a lower incidence of moderate and severe hypoglycaemia. It therefore appears that the DESMOND model had equipped patients to optimise their self-management with an intensive treatment regimen, thus providing evidence that effective education is important in helping to overcome clinical inertia. NICE has stated that a structured educational programme is recommended, with regular updates to reinforce this learning [

      NICE guideline (December 2015), Type 2 Diabetes in Adults: Management (NG28). Available at: https://www.nice.org.uk/guidance/ng28/resources/type-2-diabetes-in-adults-management-1837338615493 (last accessed 02.02.16).

      ], but the cost-effectiveness of this approach has yet to be determined.
      More basic patient education should begin as early in the disease trajectory as possible to dispel the idea that insulin represents ‘the end of the road’ [
      • Phillips P.
      Type 2 diabetes—failure: blame and guilt in the adoption of insulin therapy.
      ]. Explaining, at diagnosis, that the progressive nature of type 2 diabetes means that the majority of patients will eventually require insulin could tackle the perception that insulin therapy represents a failure in diabetes management [
      • Phillips P.
      Type 2 diabetes—failure: blame and guilt in the adoption of insulin therapy.
      ]. Indeed, the joint ADA/EASD statement does not consider insulin therapy to be the last resort, and does not denote any preference in the order of treatments after lifestyle changes and metformin [
      • Inzucchi S.E.
      • Bergenstal R.M.
      • Buse J.B.
      • et al.
      Management of hyperglycemia in type 2 diabetes: 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes.
      ].

      6.3 Tackling therapeutic barriers

      Another way in which clinical inertia is continually addressed is by the development of new therapeutic options that have minimal effect on the patient’s quality of life. In pursuit of this goal, longer-acting insulins with a lower risk of hypoglycaemia have been developed [
      • Bolli G.B.
      • DeVries J.H.
      New long-acting insulin analogs: from clamp studies to clinical practice.
      ].
      Additionally, combining insulin analogues with the newer classes of drugs has widened the options for intensification. Inhibitors of the sodium-glucose-linked transporter-2 protein (SGLT2i), which is responsible for the majority of renal glucose absorption, are the newest class of OADs to become available. They achieve a reduction in both HbA1c and body weight, and are associated with a low risk of hypoglycaemia [
      • Inzucchi S.E.
      • Bergenstal R.M.
      • Buse J.B.
      • et al.
      Management of hyperglycemia in type 2 diabetes: 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes.
      ,
      • Chao E.C.
      • Henry R.R.
      SGLT2 inhibition—a novel strategy for diabetes treatment.
      ]. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and inhibitors of the protease dipeptidyl peptidase-4 (DPP-4) are also both associated with a low risk of hypoglycaemia because of their glucose-dependent effects. Both would also be of interest to patients with concerns regarding body weight as DPP-4 inhibitors are weight-neutral and GLP-1RAs promote weight loss [
      • Inzucchi S.E.
      • Bergenstal R.M.
      • Buse J.B.
      • et al.
      Management of hyperglycemia in type 2 diabetes: 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes.
      ].
      Insulin analogues can be intensified with GLP-1RAs and vice versa to combine the clinical advantages of, and mitigate the side effects associated with, the individual components [
      • Inzucchi S.E.
      • Bergenstal R.M.
      • Buse J.B.
      • et al.
      Management of hyperglycemia in type 2 diabetes: 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes.
      ]. Fixed-ratio products, such as insulin degludec/liraglutide (IDegLira) and lixisenatide/insulin glargine (LixiLan), enable such a combination to be given with a single daily injection, simplifying the regimen for patients [
      • Gough S.C.L.
      • Bode B.W.
      • Woo V.C.
      • et al.
      One-year efficacy and safety of a fixed combination of insulin degludec and liraglutide in patients with type 2 diabetes: results of a 26-week extension to a 26-week main trial.
      ,
      • Buse J.
      • Pérez Manghi F.
      • García-Hernandez P.
      • et al.
      Insulin degludec/liraglutide (IDegLira) is superior to insulin glargine (IG) in A1c reduction, risk of hypoglycemia and weight change: DUAL V study.
      ,
      • Rosenstock J.
      • Diamant M.
      • Silvestre L.
      • et al.
      Benefits of a fixed-ratio formulation of once-daily insulin glargine/lixisenatide (LixiLan) vs. glargine in type 2 diabetes (T2DM) inadequately controlled on metformin.
      ].
      To summarise, multiple therapy options have recently become available, enabling individualisation of type 2 diabetes treatment. However, older medications that may be less effective, such as sulphonylureas [
      • Inzucchi S.E.
      • Bergenstal R.M.
      • Buse J.B.
      • et al.
      Management of hyperglycemia in type 2 diabetes: 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes.
      ,

      NICE guideline (December 2015), Type 2 Diabetes in Adults: Management (NG28). Available at: https://www.nice.org.uk/guidance/ng28/resources/type-2-diabetes-in-adults-management-1837338615493 (last accessed 02.02.16).

      ], remain in widespread use [
      • Turner L.W.
      • Nartey D.
      • Stafford R.S.
      • et al.
      Ambulatory treatment of type 2 diabetes in the U.S., 1997–2012.
      ,
      • Forst T.
      • Hanefeld M.
      • Jacob S.
      • et al.
      Association of sulphonylurea treatment with all-cause and cardiovascular mortality: a systematic review and meta-analysis of observational studies.
      ] and are promoted by the guidelines, often because of their lower costs. Physicians may resist prescribing newer, more appropriate therapies because of a lack of knowledge, experience and confidence in prescribing these medications. Therefore, it is important for post-marketing studies to focus on real-world evidence, training programmes and cost-effectiveness, and for the guidelines to be updated regularly so that they reflect the full range of therapeutic options available, to facilitate appropriate use in clinical practice.

      7. Conclusion

      Clinical inertia with insulin intensification in diabetes is a chronic problem globally, although more so in the UK, despite the availability of a wide range of new therapies as outlined in the ADA/EASD and NICE guidelines. There is insufficient focus, particularly in the new NICE guidelines, on how long a patient should remain uncontrolled before intensification of treatment. Overcoming clinical inertia also requires education of patients as to the long-term benefits of lowering their blood glucose and how best to achieve this. This will likely necessitate further education of HCPs in the form of formal training as well as professional feedback, together with increased nursing support. Finding the time, funding and human resources (particularly of nursing staff) to overcome these barriers will be the greatest challenge, particularly in the current economic and political climate, so research should continue to evaluate the most cost-effective means of tackling clinical inertia. This will encourage patients and HCPs to use the best available therapy option appropriately.

      Conflict of interest

      KK has acted as a consultant and speaker for Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Janssen, Astra Zeneca and Boehringer Ingelheim. He has received grants in support of investigator and investigator-initiated trials from Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Pfizer, Boehringer Ingelheim, Merck Sharp & Dohme, Janssen and Roche. He has also received funds for research, honoraria for speaking at meetings and has served on advisory boards for Lilly, Sanofi-Aventis, Merck Sharp & Dohme and Novo Nordisk, Boehringer Ingelheim, Janssen and Astra Zeneca.
      DM-J has been sponsored for educational lectures and served on advisory boards for Novo Nordisk, Boehringer Ingelheim–Lilly alliance, Sanofi, Takeda and Astra Zeneca.

      Funding

      The study was sponsored by Novo Nordisk, UK .

      Acknowledgements

      Medical writing and submission support were provided by Victoria Atess and Daria Renshaw of Watermeadow Medical, an Ashfield company, part of UDG Healthcare plc, funded by Novo Nordisk.
      Novo Nordisk reviewed the article for medical accuracy only.
      KK acknowledges support for this article from National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care—East Midlands (NIHR CLAHRC—EM) and the NIHR Diet, Lifestyle & Physical Activity Biomedical Research Unit based at University Hospitals of Leicester and Loughborough University. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

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