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05-14-2017 | Obesity | Review | Article

Medication use for the treatment of diabetes in obese individuals

Journal: Diabetologia

Author: John P. H. Wilding

Publisher: Springer Berlin Heidelberg


Obesity is a major cause of type 2 diabetes and may complicate type 1 diabetes. Weight loss for obese individuals with diabetes has many health benefits, often leads to improvement in glucose control and sometimes, in type 2 diabetes, near normalisation of abnormal glucose metabolism. Weight loss is difficult to maintain and attempts to lose weight may be undermined by some diabetes treatments such as sulfonylureas, thiazolidinediones and insulin. Whilst lifestyle support should be the primary approach to aid individuals who wish to lose weight, pharmacological approaches can also be considered. These include choosing glucose-lowering drugs or drug combinations that are weight neutral or result in weight loss or prescribing drugs that are specifically approved as anti-obesity medication. Given that some of the newer glucose-lowering medications that cause weight loss, such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium–glucose cotransporter 2 inhibitors (SGLT2i), are also being used or considered for use as anti-obesity drugs, it seems that the distinction between glucose-lowering medication and weight loss medication is becoming blurred. This review discusses the main pharmacological approaches that can be used to support weight loss in individuals with diabetes.
Skyler JS, Bakris GL, Bonifacio E et al (2017) Differentiation of diabetes by pathophysiology, natural history, and prognosis. Diabetes 66:241–255 CrossRefPubMed
Raum P, Lamparter J, Ponto KA et al (2015) Prevalence and cardiovascular associations of diabetic retinopathy and maculopathy: results from the Gutenberg Health Study. PLoS One 10:e0127188 CrossRefPubMedPubMedCentral
Carnethon MR (2012) Association of weight status with mortality in adults with incident diabetes. JAMA 308:2085–2085 CrossRef
Henry RR, Brechtel G, Griver K (1988) Secretion and hepatic extraction of insulin after weight-loss in obese noninsulin-dependent diabetes-mellitus. J Clin Endocrinol Metab 66:979–986 CrossRefPubMed
Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R (2011) Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 54:2506–2514 CrossRefPubMedPubMedCentral
Mingrone G, Panunzi S, De Gaetano A et al (2015) Bariatric-metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial. Lancet 386:964–973 CrossRefPubMed
Cefalu WT, Bray GA, Home PD et al (2015) Advances in the science, treatment, and prevention of the disease of obesity: reflections from a diabetes care editors’ expert forum. Diabetes Care 38:1567–1582 CrossRefPubMedPubMedCentral
The Diabetes Control and Complications Trial Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977–986 CrossRef
Bray GA, Fruhbeck G, Ryan DH, Wilding JPH (2016) Management of obesity. Lancet 387:1947–1956 CrossRefPubMed
Wing R, Bolin P, Brancati FL et al (2013) Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 369:145–154 CrossRefPubMed
Zhang P, Hire D, Espeland MA et al (2016) Impact of intensive lifestyle intervention on preference-based quality of life in type 2 diabetes: results from the Look AHEAD trial. Obesity 24:856–864 CrossRefPubMedPubMedCentral
Wing RR, Espeland MA, Clark JM et al (2016) Association of weight loss maintenance and weight regain on 4-year changes in CVD risk factors: the Action for Health in Diabetes (Look AHEAD) Clinical Trial. Diabetes Care 39:2318–2318 CrossRef
Inzucchi SE, Bergenstal RM, Buse JB et al (2015) Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 58:429–442 CrossRefPubMed
Palmer SC, Mavridis D, Nicolucci A et al (2016) Comparison of clinical outcomes and adverse events associated with glucose-lowering drugs in patients with type 2 diabetes: a meta-analysis. JAMA 316:313–324 CrossRefPubMed
Makimattila S, Nikkila K, Yki-Jarvinen H (1999) Causes of weight gain during insulin therapy with and without metformin in patients with type II diabetes mellitus. Diabetologia 42:406–412 CrossRefPubMed
Russell-Jones D, Khan R (2007) Insulin-associated weight gain in diabetes—causes, effects and coping strategies. Diabetes Obes Metab 9:799–812 CrossRefPubMed
Hirose H, Kawai T, Yamamoto Y et al (2002) Effects of pioglitazone on metabolic parameters, body fat distribution, and serum adiponectin levels in Japanese male patients with type 2 diabetes. Metabolism 51:314–317 CrossRefPubMed
Wilding J (2006) Thiazolidinediones, insulin resistance and obesity: finding a balance. Int J Clin Pract 60:1272–1280 CrossRefPubMed
Ferrannini G, Hach T, Crowe S, Sanghvi A, Hall KD, Ferrannini E (2015) Energy balance after sodium glucose cotransporter 2 (SGLT2) inhibition. Diabetes Care 38:1730–1735 CrossRefPubMedPubMedCentral
Jelsing J, Vrang N, Hansen G, Raun K, Tang-Christensen M, Knudsen LB (2012) Liraglutide: short-lived effect on gastric emptyingulong lasting effects on body weight. Diabetes Obes Metab 14:531–538 CrossRefPubMed
Turton MD, O'Shea D, Gunn I et al (1996) A role for glucagon-like peptide-1 in the central control of feeding. Nature 379:69–72 CrossRefPubMed
Pratley RE, Nauck MA, Barnett AH et al (2014) Once-weekly albiglutide versus once-daily liraglutide in patients with type 2 diabetes inadequately controlled on oral drugs (HARMONY 7): a randomised, open-label, multicentre, non-inferiority phase 3 study. Lancet Diabetes Endocrinol 2:289–297
Zachariah S, Sheldon B, Shojaee-Moradie F et al (2011) Insulin detemir reduces weight gain as a result of reduced food intake in patients with type 1 diabetes. Diabetes Care 34:1487–1491 CrossRefPubMedPubMedCentral
Frias JP, Guja C, Hardy E et al (2016) Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol 4:1004–1016 CrossRefPubMed
Wilding JPH, Bain SC (2016) Role of incretin-based therapies and sodium-glucose co-transporter-2 inhibitors as adjuncts to insulin therapy in type 2 diabetes, with special reference to IDegLira. Diabet Med 33:864–876 CrossRefPubMed
Cuthbertson DJ, Irwin A, Gardner CJ et al (2012) Improved glycaemia correlates with liver fat reduction in obese, type 2 diabetes, patients given glucagon-like peptide-1 (GLP-1) receptor agonists. PLoS One 7:e50117 CrossRefPubMedPubMedCentral
Cefalu WT, Stenlof K, Leiter LA et al (2015) Effects of canagliflozin on body weight and relationship to HbA(1c) and blood pressure changes in patients with type 2 diabetes. Diabetologia 58:1183–1187 CrossRefPubMedPubMedCentral
Pfeffer MA, Claggett B, Diaz R et al (2015) Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med 373:2247–2257 CrossRefPubMed
Zinman B, Wanner C, Lachin JM et al (2015) Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 373:2117–2128 CrossRefPubMed
Marso SP, Daniels GH, Brown-Frandsen K et al (2016) Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 375:311–322 CrossRefPubMedPubMedCentral
Marso SP, Bain SC, Consoli A et al (2016) Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 375:1834–1844 CrossRefPubMed
Liu W, Yang XJ (2016) The effect of metformin on adolescents with type 1 diabetes: a systematic review and meta-analysis of randomized controlled trials. Int J Endocrinol 2016:3854071 PubMedPubMedCentral
Dejgaard TF, Frandsen CS, Hansen TS et al (2016) Efficacy and safety of liraglutide for overweight adult patients with type 1 diabetes and insufficient glycaemic control (Lira-1): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 4:221–232 CrossRefPubMed
Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB (2015) Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care 38:1687–1693 CrossRefPubMedPubMedCentral
Ruof J, Golay A, Berne C, Collin C, Lentz J, Maetzel A (2005) Orlistat in responding obese type 2 diabetic patients: meta-analysis findings and cost-effectiveness as rationales for reimbursement in Sweden and Switzerland. Int J Obes 29:517–523 CrossRef
Davies MJ, Bergenstal R, Bode B et al (2015) Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the SCALE diabetes randomized clinical trial. JAMA 314:687–699 CrossRefPubMed
O'Neil PM, Smith SR, Weissman NJ et al (2012) Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study. Obesity 20:1426–1436 CrossRefPubMed
Hollander P, Gupta AK, Plodkowski R et al (2013) Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care 36:4022–4029 CrossRefPubMedPubMedCentral
Garvey WT, Ryan DH, Bohannon NJV et al (2014) Weight-loss therapy in type 2 diabetes: effects of phentermine and topiramate extended release. Diabetes Care 37:3309–3316 CrossRefPubMed
Janssen Research & Development (2016) Effects of co-administration of canagliflozin 300 mg and phentermine 15 mg with placebo in the treatment of non-diabetic overweight and obese participants. Available from https://​clinicaltrials.​gov/​ct2/​show/​results/​NCT02243202. Accessed 29 December 2016
Kuhnen P, Clement K, Wiegand S et al (2016) Proopiomelanocortin deficiency treated with a melanocortin-4 receptor agonist. N Engl J Med 375:240–246 CrossRefPubMed
Kim DD, Krishnarajah J, Lillioja S et al (2015) Efficacy and safety of beloranib for weight loss in obese adults: a randomized controlled trial. Diabetes Obes Metab 17:566–572 CrossRefPubMed
Rodgers RJ, Tschöp MH, Wilding JPH (2012) Anti-obesity drugs: past, present and future. Dis Models Mech 5:621–626 CrossRef
Finan B, Yang B, Ottaway N et al (2015) A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents. Nat Med 21:27–36 CrossRefPubMed
Tschöp MH, Finan B, Clemmensen C et al (2016) Unimolecular polypharmacy for treatment of diabetes and obesity. Cell Metab 24:51–62 CrossRefPubMed