Causes of weight gain during insulin therapy with and without metformin in patients with Type II diabetes mellitus

Abstract

Despite a good initial response to insulin therapy in patients with Type II (non-insulin-dependent) diabetes mellitus, long-term treatment results are often less satisfactory [1]. The poor treatment results have been attributed to the progressive nature of Type II diabetes and to failure to increase the insulin dose sufficiently to overcome insulin resistance induced by weight gain [2,3]. Previous data on the causes of weight gain during insulin therapy in patients with Type II diabetes are sparse. In one study the basal metabolic rate (BMR) was measured before and after 1 year of insulin therapy in eight patients with Type II diabetes, whose weight increased by 3.9 kg, HbA 1 c decreased by 1.7 % and absolute BMR (kJ/ min) remained unchanged [4]. BMR also remained unchanged in a study of six patients treated for 2 weeks with glyburide and insulin [5]. Glucosuria or dietary intake were not determined in these studies. Another previous study found body weight to increase by 2.1 kg during combination therapy with sulfonylurea and bedtime insulin and attributed this increase to a reduction in glucosuria but data on BMR or dietary intake were not reported [6]. Diabetologia (1999) 2 ) were treated with insulin alone (n = 13) or insulin and with metformin (n = 13). Components of energy balance (basal metabolic rate, energy intake, glucosuria) were measured at 0 and 12 months. Results. Glycaemic control improved similarly in patients using (HbA 1 c 10.5 ± 0.3 vs 7.6 ± 0.2 %, p < 0.001) and not using (10.2 ± 0.3 vs 7.8 ± 0.3 %, p < 0.001) metformin. The metformin group required 47 % less insulin than the group not using metformin (p < 0.001). Body weight increased by 3.8 ± 0.8 and 7.5 ± 1.6 kg (p < 0.05), respectively. Basal metabolic rate and glucosuria were similar at 0 and 12 months in both groups but the metformin group decreased energy intake by 1.12 ± 0.46 MJ/day, whereas it remained unchanged in the other group (0.15 ± 0.42 MJ/day). Changes in body weight and glycaemia were statistically significant independent determinants of basal metabolic rate. Their change in opposite directions explained why basal metabolic rate remained unchanged. Conclusion/interpretation. Improved glycaemia promotes weight gain by decreasing both basal metabolic rate and glucosuria. Use of metformin decreases weight gain by reducing energy intake and is therefore a useful adjunct to insulin therapy in patients with Type II diabetes. [Diabetologia (1999)

Use of a reference four-component model to define the effects of insulin treatment on body composition in type 2 diabetes: the ?Darwin study?

“…This differential body fat distribution could account for the beneficial effects of metformin in patients on insulin therapy [10,14,28,29]. Furthermore, patients who are losing significant BWt prior to insulin therapy may be more likely to gain BWt than those who are not.…”

Metformin and body weight

“…65,66 Weight gain with insulin or insulin secretagogues arises, in part, through greater retention of energy due to reduced glycosuria, along with fluid retention and an anabolic response to insulin. One evaluation of metformin in combination with insulin calculated as the change in weight per 1% decrease in HbA 1C , thus correcting for differences in glycemic control between studies.…”

“…The mechanism by which metformin may limit weight gain during insulin therapy is unclear. Reduced energy intake may be more important in this regard than changes in energy expenditure, 65,[68][69][70][71] and both metformin and insulin have been shown to modulate leptin secretion. 72,73 In summary, metformin may assist in ameliorating weight gain associated with insulin.…”

Current Therapeutic Options in Type 2 Diabetes Mellitus: A Practical Approach

“…65 The weight-neutral characteristic of metformin may be due to its ability to decrease energy intake. 66 The contribution of decreased glycosuria to weight gain can be substantial and will be greatest in those with the poorest baseline control. However, those with the poorest baseline control will improve the most with therapy.…”