Clinical Review

Individualizing Treatment of Hyperglycemia in Type 2 Diabetes

Journal of Clinical Outcomes Management. 2017 January;24(1)

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Body weight. Nearly 90% of people living with T2DM are overweight or obese. Given the close tie between obesity and T2DM, treating obesity is an obvious consideration in diabetes treatment. Major trials have shown the effectiveness of lifestyle modifications and weight reduction in delaying, prevention, and management of T2DM [4,58,59].With this in mind, clinicians should consider preferentially using antihyperglycemic agents with weight-lowering or weight-neutral effects. Among commonly used antihyperglycemic agents, metformin, GLP-1 receptor agonists, and SGLT-2 inhibitors have been shown to have weight-reduction benefits, and DPP-4 inhibitors are weight neutral. On the other hand, sulfonylureas and insulin are associated with weight gain. A systematic review and meta-analysis including 204 studies with study durations ranging from 3 months to 8 years showed comparative effects of diabetes medications with a differential effect on weight of up to 5 kg (Table 4) [60].

Metformin is associated with an average weight loss of 1.9 to 3.1 kg that was sustained with long-term use for at least 10 years in the Diabetes Prevention Program Outcomes Study [61].A systematic review of 7 randomized trials showed that in patients with T2DM, the SGLT-2 inhibitors dapagliflozin and canagliflozin were associated with weight loss (mean weighted difference of –1.81 kg and –2.3 kg, respectively) [62]. A systematic review and meta-analysis of 25 randomized controlled trials showed greater weight loss (mean weighted difference of –2.9 kg) in overweight or obese patients with or without T2DM using GLP-1 receptor agonists when compared to placebo, insulin, or oral antihyperglycemic agents [63]. Of note, the GLP-1 receptor agonist liraglutide is now approved for weight loss in patients with or without diabetes [64]. The maximum doses approved for diabetes and obesity treatment are 1.8 and 3.0 mg/day, respectively.

Since weight loss is associated with improved glycemic control, an area of emerging interest is the use of antiobesity medications for managing diabetes. Although most older weight-loss medications were only approved for short-term use, some newer agents are approved for longer-term use. Lorcaserin and the combination drugs topiramate/phentermine and naltrexone/bupropion are approved for chronic therapy, provided certain conditions are met. Patients on weight reduction agents should be monitored regularly.

If weight loss of more than 5% is not achieved after 3 months of treatment, the therapy should be discontinued. Table 6 summarizes the efficacy and characteristics of FDA-approved weight loss medications [4,37,65–68].

An even more radical departure from conventional therapy for diabetes is the consideration of metabolic, or weight-loss, surgery, which has been found to be associated with rapid and dramatic improvements in blood glucose control. Metabolic surgery has been shown to improve glucose control more effectively than any known pharmaceutical or behavioral approach. For example, in an observational study of obese patients with T2DM, bariatric surgery led to diabetes remission rates of 72.3% 2 years after surgery and 30.4% 15 years after surgery compared to 16.4% and 6.5%, respectively, in control patients [69]. With long-term follow-up, significant decreases in microvascular and macrovascular complications were seen in the surgical group [69]. Compared with medical therapy alone, bariatric surgery plus medical therapy has been associated with more weight loss, better glycemic control, less need for diabetes medications, and improved quality of life [70]. A 2016 joint statement by numerous international diabetes organizations recommends considering metabolic surgery as a treatment for T2DM and obesity [71]. American Diabetes Association guidelines recommend consideration of bariatric surgery in individuals with T2DM who have a body mass index greater than 35 kg/m ²,especially if achieving disease control is difficult by means of lifestyle modifications and medications [4].