Highlights
- •Primary care physicians are challenged with the growing complexity of treatment options.
- •This position statement recommends a simple, evidence-based cardiovascular risk stratification rubric.
- •Clinicians need to consider early combination options for patients with various common comorbidities.
- •A comprehensive summary of prescribing tips and side effects by drug class is given.
Abstract
Type 2 diabetes and its associated comorbidities are growing more prevalent, and the
complexity of optimising glycaemic control is increasing, especially on the frontlines
of patient care. In many countries, most patients with type 2 diabetes are managed
in a primary care setting. However, primary healthcare professionals face the challenge
of the growing plethora of available treatment options for managing hyperglycaemia,
leading to difficultly in making treatment decisions and contributing to therapeutic
inertia. This position statement offers a simple and patient-centred clinical decision-making
model with practical treatment recommendations that can be widely implemented by primary
care clinicians worldwide through shared-decision conversations with their patients.
It highlights the importance of managing cardiovascular disease and elevated cardiovascular
risk in people with type 2 diabetes and aims to provide innovative risk stratification
and treatment strategies that connect patients with the most effective care.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
PDF Download and 24 Hours Online AccessSubscribe:
Subscribe to Primary Care DiabetesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).Diabetes Care. 2012; 35: 1364-1379https://doi.org/10.2337/dc12-0413
- Improving primary care for patients with chronic illness: the chronic care model, part 2.JAMA. 2002; 288: 1909-1914https://doi.org/10.1001/jama.288.15.1909
- Factors influencing safe glucose-lowering in older adults with type 2 diabetes: A PeRsOn-centred ApproaCh To IndiVidualisEd (PROACTIVE) glycemic goals for older people: a position statement of primary care diabetes Europe.Primary Care Diabetes. 2019; 13: 330-352https://doi.org/10.1016/j.pcd.2018.12.005
Diabetes in Europe – Policy Puzzle, European Coalition for Diabetes, 2014. https://www.fend.org/sites/fend.org/files/ECD-PP4finalweb.pdf (accessed 06.08.19).
- IDF Diabetes Atlas.eighth edition. International Diabetes Federation, Brussels, Belgium2017
- Treatment approach to type 2 diabetes: Past, present and future.WJD. 2018; 9: 209-219https://doi.org/10.4239/wjd.v9.i12.209
- Therapeutic inertia and the legacy of dysglycemia on the microvascular and macrovascular complications of diabetes.Diabetes Care. 2019; 42: 349-351https://doi.org/10.2337/dci18-0030
- The changing face of diabetes complications.Lancet Diabetes Endocrinol. 2016; 4: 537-547https://doi.org/10.1016/S2213-8587(16)30010-9
- Evidence tips the scale toward screening for hyperglycemia.Diabetes Care. 2015; 38: 1399-1401https://doi.org/10.2337/dc15-0856
- Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017.Cardiovasc. Diabetol. 2018; 17: 83https://doi.org/10.1186/s12933-018-0728-6
- Management of hyperglycemia in Type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).Diabetes Care. 2018; 41: 2669-2701https://doi.org/10.2337/dci18-0033
- Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).Diabetologia. 2018; 61: 2461-2498https://doi.org/10.1007/s00125-018-4729-5
- Generalist solutions to complex problems: generating practice-based evidence – the example of managing multi-morbidity.BMC Fam. Pract. 2013; 14: 112https://doi.org/10.1186/1471-2296-14-112
- Barriers to effective management of type 2 diabetes in primary care: qualitative systematic review.Br. J. Gen. Pract. 2016; 66: e114-e127https://doi.org/10.3399/bjgp16X683509
- Implementation of a structured diabetes consultation model to facilitate a person-centered approach: results from a Nationwide Dutch Study.Diabetes Care. 2018; : dc171194https://doi.org/10.2337/dc17-1194
- Association between person and disease related factors and the planned diabetes care in people who receive person-centered type 2 diabetes care: an implementation study.PLOS ONE. 2019; 14: e0219702https://doi.org/10.1371/journal.pone.0219702
- Utilization of registered nurses in primary care teams: a systematic review.Int. J. Nurs. Stud. 2017; 74: 15-23https://doi.org/10.1016/j.ijnurstu.2017.05.013
- Patients with poorly controlled diabetes in primary care: healthcare clinicians’ beliefs and attitudes.Postgrad. Med. J. 2006; 82: 347-350https://doi.org/10.1136/pgmj.2005.039545
- Integrated primary care: is this the solution to the diabetes epidemic?.Diabetes Med. 2017; 34: 748-750https://doi.org/10.1111/dme.13348
- Therapeutic inertia in type 2 diabetes: prevalence, causes, consequences and methods to overcome inertia.Therap. Adv. Endocrinol. 2019; 10https://doi.org/10.1177/2042018819844694
- Therapeutic inertia in the treatment of hyperglycaemia in patients with type 2 diabetes: a systematic review.Diabetes Obes. Metab. 2018; 20: 427-437https://doi.org/10.1111/dom.13088
- Clinical inertia in general practice: widespread and related to the outcome of diabetes care.Fam Pract. 2009; 26: 428-436https://doi.org/10.1093/fampra/cmp053
- Quality of care of people with type 2 diabetes in eight European countries: Findings from the Guideline Adherence to Enhance Care (GUIDANCE) study.Diabetes Care. 2013; 36: 2628-2638https://doi.org/10.2337/dc12-1759
- Type 2 diabetes mellitus unawareness, prevalence, trends and risk factors: National Health and Nutrition Examination Survey (NHANES) 1999–2010.J. Int. Med. Res. 2017; 45: 594-609https://doi.org/10.1177/0300060517693178
- Primary care management of patients with type 2 diabetes: overcoming inertia and advancing therapy with the use of injectables.Clin. Therap. 2019; 41: 352-367https://doi.org/10.1016/j.clinthera.2018.11.015
- Achievement of guideline targets for blood pressure, lipid, and glycaemic control in type 2 diabetes: a meta-analysis.Diabetes Res. Clin. Pract. 2018; 137: 137-148https://doi.org/10.1016/j.diabres.2017.12.004
- Refill adherence and polypharmacy among patients with type 2 diabetes in general practice.Pharmacoepidemiol. Drug Saf. 2009; 18: 983-991https://doi.org/10.1002/pds.1810
- Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITION-Europe): a cluster-randomised trial.Lancet. 2011; 378: 156-167https://doi.org/10.1016/S0140-6736(11)60698-3
- Long-term effects of intensive multifactorial therapy in individuals with screen-detected type 2 diabetes in primary care: 10-year follow-up of the ADDITION-Europe cluster-randomised trial.Lancet Diabetes Endocrinol. 2019; 7: 925-937https://doi.org/10.1016/S2213-8587(19)30349-3
- Understanding the Primary Care Landscape in Europe.2019
- Diabetes research in primary care: fiction, reality or essential?.Diabetes Med. 2018; 35: 832-834https://doi.org/10.1111/dme.13638
- External validity of randomized controlled trials of glycaemic control and vascular disease: how representative are participants?.Diabetes Med. 2013; 30: 300-308https://doi.org/10.1111/dme.12047
- Sodium-glucose co-transporter 2 (SGLT2) inhibitor: comparing trial data and real-world use.Diabetes Ther. 2017; 8: 365-376https://doi.org/10.1007/s13300-017-0254-7
- How representative of a general type 2 diabetes population are patients included in cardiovascular outcome trials with SGLT2 inhibitors? A large European observational study.Diabetes Obes. Metab. 2019; 21: 968-974https://doi.org/10.1111/dom.13612
- Eligibility varies among the 4 sodium-glucose cotransporter-2 inhibitor cardiovascular outcomes trials: implications for the general type 2 diabetes US population.Am. J. Manag. Care. 2018; 24: S138-S145
S.C. Bain, A. Bakhai, M. Evans, et al., Pharmacological treatment for Type 2 diabetes integrating findings from cardiovascular outcome trials: an expert consensus in the UK, Diabetic Medicine. (n.d.). https://doi.org/10.1111/dme.14058.
- 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD.Euro. Heart J. 2019; : ehz486https://doi.org/10.1093/eurheartj/ehz486
- IDF Clinical Practice Recommendations for managing Type 2 Diabetes in Primary Care.2017 (https://www.idf.org/e-library/guidelines/128-idf-clinical-practice-recommendations-for-managing-type-2-diabetes-in-primary-care.html (accessed 14.08.19).)
- Use of consensus development to establish national research priorities in critical care.BMJ. 2000; 320: 976-980https://doi.org/10.1136/bmj.320.7240.976
WHOCC – ATC/DDD Index, (n.d.). https://www.whocc.no/atc_ddd_index/ (accessed 17.10.19).
- Poor medication adherence in type 2 diabetes: recognizing the scope of the problem and its key contributors.PPA. 2016; 10: 1299-1307https://doi.org/10.2147/PPA.S1068.21
- Shared decision making in endocrinology: present and future directions.Lancet Diabetes Endocrinol. 2016; 4: 706-716https://doi.org/10.1016/S2213-8587(15)0046.8-4
- 60 years of metformin use: a glance at the past and a look to the future.Diabetologia. 2017; 60: 1561-1565https://doi.org/10.1007/s00125-017-4343-y
- Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34).Lancet. 1998; 352: 854-865https://doi.org/10.1016/S0140-6736(98)07037-8
Scottish Intercollegiate Guidelines Network (SIGN), pharmacological management of glycaemic control in people with type 2 diabetes, 2019. https://www.sign.ac.uk/assets/sign154.pdf (accessed 09.08.19).
- Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes.Diabetologia. 2017; 60: 1620-1629https://doi.org/10.1007/s00125-017-4337-9
- Association of organic cation transporter 1 with intolerance to metformin in type 2 diabetes: a GoDARTS study.Diabetes. 2015; 64: 1786-1793https://doi.org/10.2337/db14-1388
- Glycaemic durability of an early combination therapy with vildagliptin and metformin versus sequential metformin monotherapy in newly diagnosed type 2 diabetes (VERIFY): a 5-year, multicentre, randomised, double-blind trial.Lancet. 2019; https://doi.org/10.1016/S0140-6736(19)3213.1-2
- Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add-on therapy in subjects with new-onset diabetes. Results from the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT): a randomized trial.Diabetes Obes. Metab. 2015; 17: 268-275https://doi.org/10.1111/dom.12417
- 10-year follow-up of intensive glucose control in type 2 diabetes.N. Engl. J. Med. 2008; 359: 1577-1589https://doi.org/10.1056/NEJMoa0806470
- The legacy effect in type 2 diabetes: impact of early glycemic control on future complications (The Diabetes & Aging Study).Diabetes Care. 2019; 42: 416-426https://doi.org/10.2337/dc17-1144
- Intensive glucose control in patients with Type 2 diabetes — 15-year follow-up.N. Engl. J. Med. 2019; https://doi.org/10.1056/NEJMoa.1806.802
- Improving glycaemic control in patients with Type 2 diabetes mellitus without insulin therapy.Diabetes Med. 2003; 20: 540-544https://doi.org/10.1046/j.1464-5491.2003.00980.x
- Cardiovascular diseases (CVDs).2017 (https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds) (accessed 08.08.19))
- Legacy benefits of blood glucose, blood pressure and lipid control in individuals with diabetes and cardiovascular disease: time to overcome multifactorial therapeutic inertia?.Diabetes Obes. Metab. 2018; 20: 1337-1341https://doi.org/10.1111/dom.13243
- Secondary prevention of cardiovascular diseases and application of technology for early diagnosis.BioMed Res. Int. 2018; 2018: 1-9https://doi.org/10.1155/2018/5767864
- Use of risk assessment tools to guide decision-making in the primary prevention of atherosclerotic cardiovascular disease: a special report from the american heart association and American college of cardiology.J. Am. Coll. Cardiol. 2019; 73: 3153-3167https://doi.org/10.1016/j.jacc.2018.11.005
- 10. Cardiovascular disease and risk management: standards of medical care in diabetes—2019.Diabetes Care. 2019; 42: S103-S123https://doi.org/10.2337/dc19-S010
- Development of predictive risk models for major adverse cardiovascular events among patients with type 2 diabetes mellitus using health insurance claims data.Cardiovasc. Diabetol. 2018; 17: 118https://doi.org/10.1186/s12933-018-0759-z
- Major adverse cardiovascular events in people with chronic kidney disease in relation to disease severity and diabetes status.PLOS ONE. 2019; 14https://doi.org/10.1371/journal.pone.0221.044
C. Ke, B.R. Shah, A.O. Luk, et al., Cardiovascular outcomes trials in type 2 diabetes: Time to include young adults, Diabetes Obes, Metabol, (n.d.). https://doi.org/10.1111/dom.13874.
- Complications in young adults with early-onset type 2 diabetes: losing the relative protection of youth.Diabetes Care. 2003; 26: 2999-3005https://doi.org/10.2337/diacare.26.11.2999
- Glucose control and cardiovascular disease: is it important? No.Diabetes Care. 2009; 32: S334-S336https://doi.org/10.2337/dc09-S334
- Effects of intensive glucose lowering in type 2 diabetes.N. Engl. J. Med. 2008; 358: 2545-2559https://doi.org/10.1056/NEJMoa0802743
- Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials.BMJ. 2011; 343: d4169https://doi.org/10.1136/bmj.d.4169
- Hypoglycemia and cardiovascular risk: is there a major link?.Diabetes Care. 2016; 39: S205-S209https://doi.org/10.2337/dcS15-3014
- Intensive glucose control and macrovascular outcomes in type 2 diabetes.Diabetologia. 2009; 52: 2288-2298https://doi.org/10.1007/s00125-009-1470-0
- Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials.Lancet. 2009; 373: 1765-1772https://doi.org/10.1016/S0140-6736(09)6069.7-8
- Blood pressure and stroke.Stroke. 2004; 35: 776-785https://doi.org/10.1161/01.STR. 0000116869.6477.1.5A
- Liraglutide and cardiovascular outcomes in type 2 diabetes.N. Engl. J. Med. 2016; 375: 311-322https://doi.org/10.1056/NEJMoa.1603.827
- Semaglutide and cardiovascular outcomes in patients with type 2 diabetes.N. Engl. J. Med. 2016; 375: 1834-1844https://doi.org/10.1056/NEJMoa.1607141
- Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes.N. Engl. J. Med. 2019; 381: 841-851https://doi.org/10.1056/NEJMoa.1901.118
- Rapid tightening of blood glucose control leads to transient deterioration of retinopathy in insulin dependent diabetes mellitus: the Oslo study.Br. Med. J. (Clin. Res. Ed.). 1985; 290: 811-815https://doi.org/10.1136/bmj.290.6471.811
- Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial.Lancet. 2018; 392: 1519-1529https://doi.org/10.1016/S0140-6736(18)3226.1-X
- Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial.Lancet. 2019; 394: 121-130https://doi.org/10.1016/S0140-6736(19)3114.9-3
- Lixisenatide in patients with type 2 diabetes and acute coronary syndrome.N. Engl. J. Med. 2015; 373: 2247-2257https://doi.org/10.1056/NEJMoa.1509.225
- Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes.N. Engl. J. Med. 2017; 377: 1228-1239https://doi.org/10.1056/NEJMoa.1612.917
- Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis.Lancet Diabetes Endocrinol. 2018; 6: 105-113https://doi.org/10.1016/S2213-8587(17)3041.2-6
- Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes.N. Engl. J. Med. 2015; 373: 2117-2128https://doi.org/10.1056/NEJMoa.1504.720
- Canagliflozin and cardiovascular and renal events in type 2 diabetes.N. Engl. J. Med. 2017; 377: 644-657https://doi.org/10.1056/NEJMoa.1611.925
- Dapagliflozin and cardiovascular outcomes in type 2 diabetes.N. Engl. J. Med. 2019; 380: 347-357https://doi.org/10.1056/NEJMoa.1812.389
- SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials.Lancet. 2019; 393: 31-39https://doi.org/10.1016/S0140-6736(18)3259.0-X
- Efficacy and safety of degludec versus glargine in type 2 diabetes.N. Engl. J. Med. 2017; 377: 723-732https://doi.org/10.1056/NEJMoa.1615.692
- The treatment of type 2 diabetes in heart failure.Pract. Diabetes. 2018; 35: 123-126https://doi.org/10.1002/pdi.2178
- Diabetes mellitus is associated with adverse prognosis in chronic heart failure of ischaemic and non-ischaemic aetiology.Diabetes Vasc. Dis. Res. 2013; 10: 330-336https://doi.org/10.1177/1479164112471064
- Diabetes mellitus and heart failure.Am. J. Med. 2017; 130: S40-S50https://doi.org/10.1016/j.amjmed.2017.04.010
- Prediction of heart failure in patients with type 2 diabetes mellitus- a systematic review and meta-analysis.Diabetes Res. Clin. Pract. 2015; 108: 55-66https://doi.org/10.1016/j.diabres.2015.01.011
- Association between type 2 diabetes and all-cause hospitalization and mortality in the UK general heart failure population: stratification by diabetic glycemic control and medication intensification.J. Am. Coll. Cardiol. HF. 2017; 6: 18-26https://doi.org/10.1016/j.jchf.2017.08.020
- 20-year trends in cause-specific heart failure outcomes by sex, socioeconomic status, and place of diagnosis: a population-based study.Lancet Public Health. 2019; 4: e406-e420https://doi.org/10.1016/S2468-2667(19)3010.8-2
- Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME ® trial.Eur. Heart J. 2016; 37: 1526-1534https://doi.org/10.1093/eurheartj/ehv728
- Canagliflozin and heart failure in type 2 diabetes mellitus: results from the CANVAS program.Circulation. 2018; 138: 458-468https://doi.org/10.1161/CIRCULATIONAHA.118.0342.22
- Dapagliflozin in patients with heart failure and reduced ejection fraction.N. Engl. J. Med. 2019; https://doi.org/10.1056/NEJMoa.1911303
- Lower risk of heart failure and death in patients initiated on sodium-glucose cotransporter-2 inhibitors versus other glucose-lowering drugs.Circulation. 2017; 136: 249-259https://doi.org/10.1161/CIRCULATIONAHA.117.0291.90
- Does lower limb amputation concern all SGLT2 inhibitors?.Nat. Rev. Endocrinol. 2018; 14: 326-328https://doi.org/10.1038/s41574-018-0001-9
- Efficacy and safety of sodium glucose co-transport-2 inhibitors in type 2 diabetes: a meta-analysis of randomized clinical trials: SGLT-2 inhibitors in type 2 diabetes.Diabetes Obes. Metab. 2014; 16: 457-466https://doi.org/10.1111/dom.1224.4
Janssen Pharmaceuticals, Inc., Invokana (canagliflozin) Prescribing Information, 2013, http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/INVOKANA-pi.pdf (accessed 16.08.19).
- Farxiga (dapagliflozin) Prescribing Information.2014 (https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/202293s000lbl.pdf (accessed 16.08.19).)
- Jardiance (empagliflozin) Prescribing Information.2018 (https://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf (accessed 16.08.19))
- Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial.Lancet. 2005; 366: 1279-1289https://doi.org/10.1016/S0140-6736(05)6752.8-9
- Pioglitazone and the secondary prevention of cardiovascular disease. A meta-analysis of randomized-controlled trials.Cardiovasc. Diabetol. 2017; 16: 134https://doi.org/10.1186/s12933-017-0617-4
- Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised multicentre trial.Lancet Diabetes Endocrinol. 2017; 5: 887-897https://doi.org/10.1016/S2213-8587(17)3031.7-0
- Worsening heart failure during the use of DPP-4 inhibitors.JACC: Heart Fail. 2018; 6: 445-451https://doi.org/10.1016/j.jchf.2017.12.016
- Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial.Circulation. 2014; 130: 1579-1588https://doi.org/10.1161/CIRCULATIONAHA.114.0103.89
- Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial.Lancet. 2015; 385: 2067-2076https://doi.org/10.1016/S0140-6736(14)6222.5-X
- Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes.N. Engl. J. Med. 2015; 373: 232-242https://doi.org/10.1056/NEJMoa.1501.352
- Effect of Linagliptin vs Placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial.JAMA. 2019; 321: 69-79https://doi.org/10.1001/jama.2018.1826.9
- The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man.J. Clin. Invest. 1975; 55: 845-855https://doi.org/10.1172/JCI.1079.96
- Rosiglitazone clinical trials study group. A randomized trial of rosiglitazone therapy in patients with inadequately controlled insulin-treated type 2 diabetes.Diabetes Care. 2001; 24: 1226-1232https://doi.org/10.2337/diacare.24.7.1226
- Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes.Euro. J. Heart Fail. 2018; 20: 888-895https://doi.org/10.1002/ejhf.1146
- Diabetic kidney disease: challenges, progress, and possibilities.CJASN. 2017; 12: 2032-2045https://doi.org/10.2215/CJN.11491116
- The pathobiology of diabetic complications: a unifying mechanism.Diabetes. 2005; 54: 1615-1625https://doi.org/10.2337/diabetes.54.6.1615
- The treatment of type 2 diabetes in the presence of renal impairment: what we should know about newer therapies.Clin. Pharmacol. 2016; 8: 61-81https://doi.org/10.2147/CPAA.S.8200.8
- 11. Microvascular complications and foot care: standards of medical care in diabetes—2019.Diabetes Care. 2019; 42: S124-S138https://doi.org/10.2337/dc19-S011
- Metformin therapy in patients with chronic kidney disease.Diabetes Obes. Metabol. 2012; 14: 963-965https://doi.org/10.1111/j.1463-1326.2012.0161.7.x
- Intensive glucose control improves kidney outcomes in patients with type 2 diabetes.Kidney Int. 2013; 83: 517-523https://doi.org/10.1038/ki.2012.401
- Long-term benefits of intensive glucose control for preventing end-stage kidney disease: ADVANCE-ON.Diabetes Care. 2016; 39: 694-700https://doi.org/10.2337/dc15-2322
- Diabetes treatment in patients with renal disease: is the landscape clear enough?.World J. Diabetes. 2014; 5: 651-658https://doi.org/10.4239/wjd.v5.i5.651
- The place of gliclazide MR in the evolving type 2 diabetes landscape: a comparison with other sulfonylureas and newer oral antihyperglycemic agents.Diabetes Res. Clin. Pract. 2018; 143: 1-14https://doi.org/10.1016/j.diabres.201805.028
- Management of hyperglycemia in diabetic kidney disease.Diabetes Spectrum. 2015; 28: 214-219https://doi.org/10.2337/diaspect.28.3.214
- Review of glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes mellitus in patients with chronic kidney disease and their renal effects.J. Diabetes. 2019; https://doi.org/10.1111/1753-0407.1296.9
- Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition.Diabetologia. 2017; 60: 215-225https://doi.org/10.1007/s00125-016-4157-3
- Empagliflozin and progression of kidney disease in type 2 diabetes.N. Engl. J. Med. 2016; 375: 323-334https://doi.org/10.1056/NEJMoa.1515920
- Canagliflozin and renal outcomes in type 2 diabetes and nephropathy.N. Engl. J. Med. 2019; 380: 2295-2306https://doi.org/10.1056/NEJMoa.1811.744
- Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE–TIMI 58 randomised trial.Lancet Diabetes Endocrinol. 2019; 7: 606-617https://doi.org/10.1016/S2213-8587(19)3018.0-9
- Prevalence of and trends in diabetes among adults in the United States, 1988–2012.JAMA. 2015; 314: 1021-1029https://doi.org/10.1001/jama.2015.10029
- Health effects of overweight and obesity in 195 countries over 25 years.N. Engl. J. Med. 2017; 377: 13-27https://doi.org/10.1056/NEJMoa1614362
- The metabolic syndrome.Endocr. Rev. 2008; 29: 777-822https://doi.org/10.1210/er.2008-0024
- What causes the insulin resistance underlying obesity?.Curr. Opin. Endocrinol. Diabetes Obes. 2012; 19: 81-87https://doi.org/10.1097/MED.0b013e.3283.514e13
- Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables.Lancet Diabetes Endocrinol. 2018; 6: 361-369https://doi.org/10.1016/S2213-8587(18)3005.1-2
- Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction.N. Engl. J. Med. 1998; 339: 229-234https://doi.org/10.1056/NEJM199807233390.404
- Primary prevention of cardiovascular disease in diabetes mellitus.J. Am. Coll. Cardiol. 2017; 70: 883-893https://doi.org/10.1016/j.jacc.2017.07.001
- Severe hypoglycemia and risks of vascular events and death.N. Engl. J. Med. 2010; 363: 1410-1418https://doi.org/10.1056/NEJMoa.1003.795
- Glucose control and vascular outcomes in type 2 diabetes: is the picture clear?.Diabetes Care. 2016; 39: S187-S195https://doi.org/10.2337/dcS15-3023
- The effect of oral antidiabetic agents on A1C levels: a systematic review and meta-analysis.Diabetes Care. 2010; 33: 1859-1864https://doi.org/10.2337/dc09-1727
- Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy.N. Engl. J. Med. 2006; 355: 2427-2443https://doi.org/10.1056/NEJMoa.066224
- Long-term efficacy and safety comparison of liraglutide, glimepiride and placebo, all in combination with metformin in type 2 diabetes: 2-year results from the LEAD-2 study.Diabetes Obes. Metab. 2013; 15: 204-212https://doi.org/10.1111/dom.1201.2
- Empagliflozin compared with glimepiride in metformin-treated patients with type 2 diabetes: 208-week data from a masked randomized controlled trial.Diabetes Obes. Metab. 2018; 20: 2768-2777https://doi.org/10.1111/dom.1345.7
- The association between sulfonylurea use and all-cause and cardiovascular mortality: a meta-analysis with trial sequential analysis of randomized clinical trials.PLoS Med. 2016; 13https://doi.org/10.1371/journal.pmed.1001.992
- Effect of linagliptin vs glimepiride on major adverse cardiovascular outcomes in patients with type 2 diabetes: the CAROLINA randomized clinical trial.JAMA. 2019; 322: 1155-1166https://doi.org/10.1001/jama.2019.1377.2
- Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).Lancet. 1998; 352: 837-853
- The infamous, famous sulfonylureas and cardiovascular safety: much ado about nothing?.Curr. Diabetes Rep. 2017; 17: 124https://doi.org/10.1007/s11892-017-0954-4
- Efficacy of gliclazide in comparison with other sulphonylureas in the treatment of NIDDM.Diabetes Res. Clin. Pract. 1991; 14: S65-S67https://doi.org/10.1016/0168-8227(91)9001.0-B
- Hypoglycaemia when adding sulphonylurea to metformin: a systematic review and network meta-analysis.Br. J. Clin. Pharmacol. 2016; 82: 1291-1302https://doi.org/10.1111/bcp.1305.9
- Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.N. Engl. J. Med. 2008; 358: 2560-2572https://doi.org/10.1056/NEJMoa.0802987
- Clinical evaluation of glimepiride versus glyburide in NIDDM in a double-blind comparative study. Glimepiride/Glyburide Research Group.Horm. Metab. Res. 1996; 28: 426-429https://doi.org/10.1055/s-2007-9798.31
- Availability and affordability of essential medicines for diabetes across high-income, middle-income, and low-income countries: a prospective epidemiological study.Lancet Diabetes Endocrinol. 2018; 6: 798-808https://doi.org/10.1016/S2213-8587(18)3023.3-X
- Mortality risk among sulfonylureas: a systematic review and network meta-analysis.Lancet Diabetes Endocrinol. 2015; 3: 43-51https://doi.org/10.1016/S2213-8587(14)7021.3-X
- A systematic review and meta-analysis of hypoglycemia and cardiovascular events: a comparison of glyburide with other secretagogues and with insulin.Diabetes Care. 2007; 30: 389-394https://doi.org/10.2337/dc06-1789
- The right place for Sulphonylureas today: part of review the series: implications of recent CVOTs in Type 2 diabetes mellitus.Diabetes Res. Clin. Pract. 2019; : 107836https://doi.org/10.1016/j.diabres.2019.1078.36
- The role of nateglinide and repaglinide, derivatives of meglitinide, in the treatment of type 2 diabetes mellitus.Arch. Med. Sci. 2013; 9: 936-943https://doi.org/10.5114/aoms.2013.3499.1
- Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study, Eur.Heart. J. 2011; 32: 1900-1908https://doi.org/10.1093/eurheartj/ehr077
- Efficacy and safety of pioglitazone versus metformin in patients with type 2 diabetes mellitus: a double-blind, randomized trial.J. Clin. Endocrinol. Metab. 2004; 89: 6068-6076https://doi.org/10.1210/jc.2003-0308.61
- Long-term efficacy and tolerability of add-on pioglitazone therapy to failing monotherapy compared with addition of gliclazide or metformin in patients with type 2 diabetes.Diabetologia. 2005; 48: 1093-1104https://doi.org/10.1007/s00125-005-1751-1
- Thiazolidinediones and blood lipids in type 2 diabetes.Arterioscler. Thromb. Vasc. Biol. 2003; 23: 1744-1749https://doi.org/10.1161/01.ATV. 0000090521.25968.4D
- Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials.JAMA. 2007; 298: 1180-1188https://doi.org/10.1001/jama.298.10.1180
- Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial.JAMA. 2008; 299: 1561-1573https://doi.org/10.1001/jama.299.13.1561
- Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial.JAMA. 2006; 296: 2572-2581https://doi.org/10.1001/jama.296.21.joc.6015.8
- Pioglitazone, vitamin e, or placebo for nonalcoholic steatohepatitis.N. Engl. J. Med. 2010; 362: 1675-1685https://doi.org/10.1056/NEJMoa.0907.929
- Role of insulin resistance and diabetes in the pathogenesis and treatment of nonalcoholic fatty liver disease.Curr. Hepatol. Rep. 2014; 13: 159-170https://doi.org/10.1007/s11901-014-0229-3
- Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association.Diabetes Care. 2004; 27: 256-263https://doi.org/10.2337/diacare.27.1.256
- Effect of thiazolidinediones on body weight in patients with diabetes mellitus.Am. J. Med. 2003; 115: 42S-48Shttps://doi.org/10.1016/j.amjmed.2003.09.005
- Thiazolidinediones and fracture risk in patients with Type 2 diabetes.Diabetes Med. 2011; 28: 759-771https://doi.org/10.1111/j.1464-5491.2010.03187.x
- Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study.Diabetes Care. 2011; 34: 916-922https://doi.org/10.2337/dc10-1068
- Acarbose: safe and effective for lowering postprandial hyperglycaemia and improving cardiovascular outcomes.Open Heart. 2015; 2https://doi.org/10.1136/openhrt-2015-0003.27
- Comparison of the hypoglycemic effect of acarbose monotherapy in patients with type 2 diabetes mellitus consuming an Eastern or Western diet: a systematic meta-analysis.Clin. Ther. 2013; 35: 880-899https://doi.org/10.1016/j.clinthera.2013.03.020
- Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: The STOP-NIDDM trial.JAMA. 2003; 290: 486-494https://doi.org/10.1001/jama.290.4.486
- Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double-blind, placebo-controlled trial.Lancet Diabetes Endocrinol. 2017; 5: 877-886https://doi.org/10.1016/S2213-8587(17)3030.9-1
- Alpha-glucosidase inhibitors for patients with type 2 diabetes: results from a Cochrane systematic review and meta-analysis.Diabetes Care. 2005; 28: 154-163https://doi.org/10.2337/diacare.28.1.154
Novo Nordisk A/S, Victoza (liraglutide) Prescribing Information, 2019. https://www.novo-pi.com/victoza.pdf (accessed 16.08.19).
Novo Nordisk A/S, Ozempic (semaglutide) Prescribing Information, 2019. Available from: https://www.novo-pi.com/ozempic.pdf.
- Effects of liraglutide compared with placebo on events of acute gallbladder or biliary disease in patients with type 2 diabetes at high risk for cardiovascular events in the LEADER randomized trial.Diabetes Care. 2019; https://doi.org/10.2337/dc19-0415
- Can we exonerate GLP-1 receptor agonists from blame for adverse pancreatic events?.Ann. Transl. Med. 2018; 6: 186https://doi.org/10.21037/atm.2018.03.06
- Impact of GLP-1 receptor agonists on blood pressure, heart rate and hypertension among patients with type 2 diabetes: A systematic review and network meta-analysis.Diabetes Res. Clin. Pract. 2015; 110: 26-37https://doi.org/10.1016/j.diabres.2015.07.015
M. Mazidi, P. Rezaie, H.-K. Gao, A.P. Kengne, Effect of sodium-glucose cotransport-2 inhibitors on blood pressure in people with type 2 diabetes mellitus: a systematic review and meta-analysis of 43 randomized control trials with 22 528 patients, J. Am. Heart Assoc. 6 (n.d.) e004007. https://doi.org/10.1161/JAHA.116.004007.
- Prevalence and incidence of hypoglycaemia in 532,542 people with type 2 diabetes on oral therapies and insulin: a systematic review and meta-analysis of population based studies.PLOS ONE. 2015; 10: e0126427https://doi.org/10.1371/journal.pone.0126.427
- Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes. HOE 901/3002 Study Group.Diabetes Care. 2000; 23: 1130-1136https://doi.org/10.2337/diacare.23.8.1130
- A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with nph insulin as add-on therapy to oral glucose-lowering drugs in insulin-naïve people with type 2 diabetes.Diabetes Care. 2006; 29: 1269-1274https://doi.org/10.2337/dc05-1365
- Effect of insulin degludec vs insulin glargine U100 on hypoglycemia in patients with type 2 diabetes: the SWITCH 2 randomized clinical trial.JAMA. 2017; 318: 45-56https://doi.org/10.1001/jama.2017.7117
- New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using basal and mealtime insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 1).Diabetes Care. 2014; 37: 2755-2762https://doi.org/10.2337/dc14-0991
- Efficacy and safety of LixiLan, a titratable fixed-ratio combination of insulin glargine plus lixisenatide in type 2 diabetes inadequately controlled on basal insulin and metformin: The LixiLan-L randomized trial.Diabetes Care. 2016; 39: 1972-1980https://doi.org/10.2337/dc16-1495
- Efficacy and safety of IDegLira versus basal-bolus insulin therapy in patients with type 2 diabetes uncontrolled on metformin and basal insulin; DUAL VII randomized clinical trial.Diabetes Care. 2018; : dc171114https://doi.org/10.2337/dc17-1114
- Metformin treatment of type 2 diabetes mellitus in pregnancy: update on safety and efficacy.Therap. Adv. Drug Saf. 2018; 9: 287-295https://doi.org/10.1177/2042098618769831
- Abdominal obesity, insulin resistance, and cardiovascular risk in pre-diabetes and type 2 diabetes.Eur. Heart J. Suppl. 2006; 8: B20-B25https://doi.org/10.1093/eurheartj/sul004
- Targeting weight loss interventions to reduce cardiovascular complications of type 2 diabetes: a machine learning-based post-hoc analysis of heterogeneous treatment effects in the Look AHEAD trial.Lancet Diabetes Endocrinol. 2017; 5: 808-815https://doi.org/10.1016/S2213-8587(17)3017.6-6
- Heterogeneity of treatment effects from an intensive lifestyle weight loss intervention on cardiovascular events in patients with type 2 diabetes: data from the look AHEAD trial.Diabetes Care. 2019; 42: 1988-1994https://doi.org/10.2337/dc19-0776
- Effects of moderate and subsequent progressive weight loss on metabolic function and adipose tissue biology in humans with obesity.Cell Metab. 2016; 23: 591-601https://doi.org/10.1016/j.cmet.2016.02.005
- Weight management in type 2 diabetes: current and emerging approaches to treatment.Diabetes Care. 2015; 38: 1161-1172https://doi.org/10.2337/dc14-1630
- Epidemiology of diabetes and diabetes complications in the elderly: an emerging public health burden.Curr. Diab. Rep. 2013; 13https://doi.org/10.1007/s11892-013-0425-5
- Where frailty meets diabetes: frailty and diabetes.Diabetes Metab. Res. Rev. 2016; 32: 261-267https://doi.org/10.1002/dmrr.2743
- 12. Older adults: standards of medical care in diabetes—2019.Diabetes Care. 2019; 42: S139-S147https://doi.org/10.2337/dc19-S012
- Sarcopenia and diabetes: hyperglycemia is a risk factor for age-associated muscle mass and functional reduction.J. Diabetes Investig. 2015; 6: 623-624https://doi.org/10.1111/jdi.1236.5
- Obesity paradox does exist.Diabetes Care. 2013; 36: S276-S281https://doi.org/10.2337/dcS13-2023
- Postprandial blood glucose is associated with generalized pruritus in patients with type 2 diabetes.Eur. J. Dermatol. 2013; 23: 688-693https://doi.org/10.1684/ejd.2013.2100
- Urinary tract infections in patients with type 2 diabetes mellitus: review of prevalence, diagnosis, and management.Diabetes Metab. Syndr. Obes. 2015; 8: 129-136https://doi.org/10.2147/DMSO.S.5179.2
- Treatment of diabetes in older adults: an endocrine society clinical practice guideline.J. Clin. Endocrinol. Metab. 2019; 104: 1520-1574https://doi.org/10.1210/jc.2019-0019.8
- European diabetes working party for older people 2011 clinical guidelines for type 2 diabetes mellitus. Executive Summary.Diabetes Metab. 2011; 37: S27-S38https://doi.org/10.1016/S1262-3636(11)70962-4
- A randomized controlled trial comparing efficacy and safety of insulin glargine 300 units/ml versus 100 units/ml in older people with type 2 diabetes: results from the SENIOR study.Diabetes Care. 2018; 41: 1672-1680https://doi.org/10.2337/dc18-0168
- Management of diabetes in older adults.Nutr. Metabol. Cardiovas. Dis. 2018; 28: 206-218https://doi.org/10.1016/j.numecd.2017.11.007
The European Definition of GP/FM | WONCA Europe, (n.d.). https://www.woncaeurope.org/gp-definitions (accessed 18.10.19).
- Glucophage Product Monograph.2018 (http://products.sanofi.ca/en/glucophage.pdf (accessed 16.08.19))
- Effectiveness of progressive dose-escalation of exenatide(exendin-4) in reducing dose-limiting side effects in subjects with type 2 diabetes.Diabetes Metab. Res. Rev. 2004; 20: 411-417https://doi.org/10.1002/dmrr.499
- Genital and urinary tract infections in diabetes: Impact of pharmacologically-induced glucosuria.Diabetes Res. Clin. Pract. 2014; 103: 373-381https://doi.org/10.1016/j.diabres.2013.12.052
- Sodium glucose cotransporter 2 inhibitors and risk of genital mycotic and urinary tract infection: A population-based study of older women and men with diabetes.Diabetes Obes. Metabol. 2019; 21: 2394-2404https://doi.org/10.1111/dom.1382.0
- An update on sodium-glucose co-transporter-2 inhibitors for the treatment of diabetes mellitus.Curr. Opin. Endocrinol. Diabetes Obes. 2017; : 1https://doi.org/10.1097/MED.0000000000000311
- Assessing bladder cancer risk in type 2 diabetes clinical trials: the dapagliflozin drug development program as a ‘case study’.Diabetes Ther. 2015; 6: 357-375https://doi.org/10.1007/s13300-015-0128-9
jardiance-epar-product-information_en.pdf, (n.d.). https://www.ema.europa.eu/en/documents/product-information/jardiance-epar-product-information_en.pdf (accessed 22.04.20).
Merck & Co., Inc, Januvia (sitagliptin) Prescribing Information, 2019. https://www.merck.com/product/usa/pi_circulars/j/januvia/januvia_pi.pdf (accessed 16.08.19).
- Onglyza (saxagliptin) Prescribing Information.2009 (https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022350lbl.pdf (accessed 16.08.19))
- Tradjenta (linagiptin) Prescribing Information.2019 (https://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Tradjenta/Tradjenta.pdf (accessed 06.08.19))
- State of the art paper Sulfonylureas and their use in clinical practice.AOMS. 2015; 4: 840-848https://doi.org/10.5114/aoms.2015.5330.4
- Pharmacokinetics of glibenclamide and its metabolites in diabetic patients with impaired renal function.Euro. J. Clin. Pharmacol. 1998; 53: 429-435https://doi.org/10.1007/s002280050403
- Pioglitazone: side effect and safety profile.Expert Opin. Drug Safety. 2010; 9: 347-354https://doi.org/10.1517/1474033100362321.8
- Antihyperglycemic medications and cardiovascular risk reduction.Eur. Endocrinol. 2017; 13: 86-90https://doi.org/10.17925/EE.201713.02.86
- Cardiovascular outcomes trials in type 2 diabetes: where do we go from here? Reflections from a diabetes care editors’ expert forum.Diabetes Care. 2018; 41: 14-31https://doi.org/10.2337/dci17-0057
- Alogliptin after acute coronary syndrome in patients with type 2 diabetes.N. Engl. J. Med. 2013; 369: 1327-1335https://doi.org/10.1056/NEJMoa.1305.889
- Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus.N. Engl. J. Med. 2013; 369: 1317-1326https://doi.org/10.1056/NEJMoa.1307.684
- Cardiovascular safety and renal microvascular outcome with linagliptin in patients with T2D at high vascular risk.2019 (https://adahighlights2019.com/articles/carolina-trial/read (accessed 04.09.19))
Article Info
Publication History
Published online: June 09, 2020
Accepted:
May 11,
2020
Received in revised form:
April 30,
2020
Received:
January 15,
2020
Identification
Copyright
© 2020 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
