Metformin increases plasma ghrelin in Type 2 diabetes


Professor Evan Begg, Clinical Pharmacology, Department of Medicine, University of Otago–Christchurch, Private Bag 4345, Christchurch 8041, New Zealand.
Tel:+ 64 3 364 1055
Fax:+ 64 3 364 1003



• Metformin, unlike the other major antihyperglycaemic drugs, is not associated with weight gain.

• Ghrelin is an appetite-stimulating hormone whose concentrations vary in relation to food, obesity and diabetes control.

• Reports are conflicting about how metformin affects ghrelin concentrations, and this study was aimed at resolving this issue in patients with Type 2 diabetes.


• In this study an increase in ghrelin concentrations was seen in response to metformin treatment in patients with Type 2 diabetes.

• This effect was opposite to what might be expected if the effect of metformin on weight control was mediated via suppression of ghrelin.

• It is likely that the ghrelin response was secondary to improved glycaemic control.

• Meal time changes in appetite and satiety did not correlate with changes in ghrelin, which suggests ghrelin may not be important in meal initiation.

AIMS Metformin treatment of Type 2 diabetes is not usually associated with weight gain, and may assist with weight reduction. Plasma ghrelin concentrations are inversely associated with obesity and food intake. Metformin might therefore affect ghrelin concentrations, although previous studies have shown variable results in this regard. The primary aim of this study was to determine the effect of metformin on plasma ghrelin, appetite and satiety in patients with Type 2 diabetes.

METHODS Eighteen patients with Type 2 diabetes were studied before and after 6 weeks of metformin treatment, which was titrated to 1 g b.d. On the study days patients were fed standard meals of 390 kcal at 08.00 and 12.30 h, plasma samples were collected at 15- and 30-min intervals, and appetite and satiety were measured on visual analogue scales. Changes in the area under the concentration–time curves (AUCs) of plasma ghrelin, insulin, glucose, appetite and satiety were assessed and examined for correlations with metformin AUCs. Changes in fasting adiponectin and leptin were also measured.

RESULTS Treatment with metformin increased the mean AUC (07.30–16.30 h) of plasma ghrelin by 24% (P= 0.003), while decreasing those of glucose by 19% (P < 0.001) and insulin by 19% (P= 0.001). No changes were detected in hunger and satiety, or in fasting adiponectin or leptin concentrations. There were no clear correlations between metformin plasma concentrations (AUC) and changes in plasma glucose, insulin or ghrelin.

CONCLUSIONS Treatment of Type 2 diabetes with metformin was associated with increased plasma ghrelin concentrations, without associated changes in hunger and satiety.