Bodyweight Changes Associated with Antihyperglycaemic Agents in Type 2 Diabetes Mellitus

Abstract

The majority of patients with type 2 diabetes mellitus are overweight or obese at the time of diagnosis, and obesity is a recognised risk factor for type 2 diabetes and coronary heart disease (CHD). Conversely, weight loss has been shown to improve glycaemic control in patients with type 2 diabetes, as well as to lower the risk of CHD. The traditional pharmacotherapies for type 2 diabetes can further increase weight and this may undermine the benefits of improved glycaemic control. Furthermore, patients' desire to avoid weight gain may jeopardise compliance with treatment, thereby limiting treatment success and indirectly increasing the risk of long-term complications. This review evaluates the influences of established and emerging therapies on bodyweight in type 2 diabetes. Improvement in glycaemic control with insulin secretagogues has been associated with weight gain. On the other hand, biguanides such as metformin have been consistently shown to have a beneficial effect on weight; metformin appears to modestly reduce weight when used as a monotherapy. alpha-Glucosidase inhibitors are considered weight neutral; in fact, the results of some studies show that they cause reductions in weight. Thiazolidinediones (TZDs) are typically associated with weight gain and increased risk of oedema, while the impact of some TZDs, such as pioglitazone, on lipid homeostasis could be beneficial. Insulin, the most effective therapy when oral agents are ineffective, has always been linked to significant weight gain. Newly developed insulin analogues can lower the risk of hypoglycaemia compared with human insulin, but most have no advantage in terms of weight gain. The basal analogue insulin detemir, however, has been demonstrated to cause weight gain to a lesser extent than human insulin. The emerging treatments, such as glucagon-like peptide-1 agonists and the amylin analogue, pramlintide, seem able to decrease weight in patients with type 2 diabetes, whereas dipeptidyl peptidase-4 inhibitors seem to be weight neutral. In summary, while reduction of hyperglycaemia remains the foremost goal in the treatment of patients with type 2 diabetes, the avoidance of weight gain may be a clinically important secondary goal. This is already possible with careful selection of available therapies, while several emerging therapies promise to further extend the options available.

Risk of cardiovascular disease and mortality in overweight and obese patients with type 2 diabetes: an observational study in 13,087 patients

“…It also showed that patients who gained most weight during the study (median BMI change+3.8 kg/m 2 ) had a 1.8-to 2.3-fold increase in risk of CHD compared with those who gained less weight or who lost weight. Weight change with regard to diabetes is a complex topic, as weight loss could reflect poorly controlled diabetes (few in this study), and weight gain could be attributable to pharmacological treatment to improve metabolic control [34]. The latter was accounted for by adjusting for the type of hypoglycaemic treatment.…”

Combating the dual burden: therapeutic targeting of common pathways in obesity and type 2 diabetes

“…While reduction of hyperglycaemia remains the foremost goal in the pharmacological treatment of T2DM, the avoidance of weight gain may be a clinically important secondary goal 20 .…”

Present status of sulfonylurea treatment for type 2 diabetes in Japan: Second report of a cross-sectional survey of 15,652 patients

“…This suggests that, for Japanese T2DM patients, the addition of either biguanide or TZD to sulfonylurea does not necessarily improve glycemic control. It has been reported that the metformin monotherapy reduced body weight and reversed the weight gain by sulfonylurea in combination with sulfonylurea, while BMI of the patients treated with sulfonylurea alone compared with sulfonylurea plus metformin was variable [26,27]. Our study was not longitudinal and could not detect the changes in body weight, therefore, we could not discuss the desirable effect of metformin on BMI.…”