Since some 80-90% of people with type 2 diabetes are overweight or obese, it’s important to understand which pharmacotherapies exist for weight management.
By Shelley Diamond, BScPhm
Illustration by Martin Bregman
A prospective study1 has demonstrated that each 5kg/m2 higher body mass index (BMI) above 25 kg/m2 was associated with about 30% higher overall mortality. On the other hand, a recent meta-analysis2 has shown that a weight loss of 5.5kg in obese adults may be associated with approximately a 15% reduction in all-cause mortality.
Lifestyle intervention including low-calorie diets and regular physical activity are the main recommendations for people with type 2 dibaetes, but it’s difficult for most patients to lose adequate body weight to reach their glycemic and metabolic targets, and hard to sustain over time. Pharmacotherapy is, therefore, a reasonable option for many patients to reach these goals, and generally considered for people with BMI ≥30.0 kg/m2 with no obesity-related comorbidities or risk factors, or for those with BMI ≥27.0 kg/m2 with obesity-related comorbidities or risk factors.3
Current therapeutic options for weight management
GLUCOSE-LOWERING MEDICATIONS WHICH CAUSE WEIGHT LOSS
Metformin has been shown to be weight neutral or associated with a weight loss of approximately 3kg.
Glucagon-like peptide-1 receptors agonists (GLP-1 RAs)
These particular medications raise GLP-1, an incretin hormone, to levels which cause a central inhibitory effect on appetite and food intake. A meta-analysis of 25 clinical studies4 showed they resulted in an average weight loss of 2.8kg. A head-to-head comparison5 between liraglutide 1.8mg daily and exenatide 10mcg twice daily demonstrated that liraglutide had greater glycemic efficacy and therefore greater weight loss, compared to exenatide. Both medications had similar side effect profiles. Newer GLP-1 RAs, albiglutide and dulaglutide, have similar glycemic efficacy but less weight reduction compared to liraglutide.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors
Currently canagliflozin, dapagliflozin and empagliflozin are available in Canada. As a result of their glucosuria, SGLT2 inhibitors also cause fewer calories to be reabsorbed, and this causes a sustained weight loss (up to two years) of approximately 3-5 kg. These medications can be used as monotherapy or in combination with other antihyperglycemic agents for the purpose of weight loss.
Orlistat, an intestinal lipase inhibitor, is approved for the indication of long-term weight management and for glycemic treatment in people with type 2 diabetes. It reduces dietary fat digestion and absorption by about 30%. A meta-analysis6 showed that orlistat reduced body weight by 2.9kg in overweight and obese subjects. In a systematic review7 of seven weight-loss clinical trials in people with type 2 diabetes, orlistat was found to cause an excess of 2kg weight loss or 2.3% baseline weight, as well as significant reductions in A1C, lipids and blood pressure. Several limiting side effects prevent it from being prescribed by healthcare providers, including flatulence, fecal urgency and oily stools.
The second antiobesity agent approved by Health Canada in recent years is liraglutide. The effect on weight loss is dose-dependent (up to 3.0mg once daily). Improvement in cardiometabolic risk factors and health-related quality of life scores have been seen in several clinical trials, and it reduces A1C levels to a great extent than orlistat. Side effects have included mild and transient nausea and diarrhea.
The options for weight management will continue to expand, as there are several new drugs likely to become available in Canada in the next few years. Bariatric surgery, a non-pharmacologic option, has also been extremely successful for the management of severe obesity. After having many years with very limited weight management options, the doors are opening with effective choices.
- Prospective Studies Collaboration, Whitlock G, Lewington S, et al. Body-mass index and cause-specific mortality in 900,000 adults: Collaborative analyses of 57 prospective studies. Lancet 2009;373:1083-96.
- Kritchevsky SB, Beavers KM, Miller ME, et al. Intentional weight loss and all-cause mortality: A meta-analysis of randomized clinical trials. PLoS ONE 2015;10:e0121993
- National Institutes of Health Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report Obes Res 6 suppl 2 1998 51S 209S.
- Vilsbøll T, Christensen M, Junker AE, et al. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ 2012;344:d7771.
- Buse JB, Rosenstock J, Sesti G, et al. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomized parallel-group, multinational, open-label trial (LEAD-6). Lancet 2009;374:39-47.
- Padwal R, Rucker D, Li S, et al. Long-term pharmacotherapy for obesity and overweight. Cochrane Database Syst Rev 2003;(4):CD004094.
- Norris SL, Zhang X, Avenell A, et al. Pharmacotherapy for weight loss in adults with type 2 diabetes mellitus. Cochrane Database Syst Rev 2005;(1):CD004096.