Effect of weight‐reducing agents on glycaemic parameters and progression to Type 2 diabetes: a review

Abstract

Weight loss is associated with improvements in glycaemic control and cardiovascular disease risk factors. However, in the diabetic population, weight management is more challenging, in part because of the weight-promoting effects of the majority of glucose-lowering therapies. This review summarizes evidence from 23 placebo-controlled randomized trials, of at least 1 year duration, on the effects of drugs promoting weight loss (orlistat, sibutramine and rimonabant) on glycaemic variables, diabetes incidence and diabetes control. Fifteen studies of non-diabetic subjects were found, eight of which included a longer treatment period. Eight studies in diabetic patients were reviewed. In non-diabetic subjects, weight loss agents led to a significant improvement in fasting glucose, fasting insulin and insulin resistance. In the diabetic population, glycated haemoglobin decreased by 0.28-1.1% with orlistat and 0.6% with sibutramine and rimonabant. Orlistat reduces progression to diabetes in patients with glucose intolerance treated for 4 years (risk reduction of 45%). In summary, despite leading to only modest weight loss after 12 months, agents promoting weight loss have beneficial effects on glycaemic parameters, glycaemic control and progression to diabetes. These additional benefits of weight loss agents need to be highlighted in order to increase their judicious use in clinical practice, although this may be limited by their well-known adverse side effects. The longer-term safety of these agents beyond a few years is yet to be established.

Weight Management in Overweight and Obese Patients with Type 2 Diabetes Mellitus

“…[9][10][11] Furthermore, in patients who have already been diagnosed with type 2 diabetes, weight loss may help slow the natural history of the disease and delay the need for intensification of therapy to insulin. [10][11][12] However, weight reduction in overweight and obese patients with type 2 diabetes can prove challenging. Typically these patients lose less weight and at slower rates than non-diabetic individuals, due to metabolic dysregulation, potential comorbidities that restrict physical activity and a lack of dietary adherence.…”

Cardiovascular Risk-Benefit Profile of Sibutramine

“…[10,12] One of the common health consequences of abdominal obesity is type 2 diabetes mellitus (T2DM) and antiobesity management is a prerequisite in preventing diabetes and treating diabetic patients. [5,13,14] Weight reduction in obese persons will improve hyperglycaemia and will reduce all of the CVD risk factors associated with T2DM. However, no long-term, large-scale study of intentional weight loss with medical means has been adequately powered to examine CVD endpoints in individuals with or without diabetes.…”

Oral Antidiabetic Agents

“…It is also pertinent to note the link between postprandial hyperglycemic excursions and cardiovascular risk, which mandates the need to also address this component of the hyperglycemic day profi le [27] . Additionally, consideration should be given to the improvements in glycemic control that can be achieved through the treatment of obesity (see Chapter 14 ) [28] . By the time of diagnosis, insulin resistance is usually well established and does not usually progress with extended duration of the disease [8] .…”

“…In overweight and obese patients with T2DM this typically increases weight reduction by an extra 2 -3 kg, and additional reductions in HbA 1c of 0.28 -1.1% (3 -12 mmol/mol) have been reported [28] . Potential improvements in the glucose -fatty acid cyle might be envisaged.…”