The effect of obesity on glycaemic response to metformin or sulphonylureas in Type 2 diabetes

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Abstract
In treating Type 2 diabetes (T2DM), UK guidelines recommend metformin in obese and overweight patients, and either sulphonylureas or metformin in normal weight patients. Although other factors influence prescribing choice, a key objective in treating T2DM is to lower plasma glucose. There is little data on how glycaemic response to oral agents varies with body mass index (BMI). Therefore, we assessed current prescribing practice and effect of BMI on glycaemic response to sulphonylureas and metformin in a large population T2DM cohort. BMI was determined in 3856 T2DM patients on sulphonylurea or metformin monotherapy in 2001-2002. Patients were identified from the Diabetes Audit and Research in Tayside, Scotland (DARTS) database. In a linear regression, the effect of BMI and other confounders on drug response was assessed in 2064 treatment-naïve patients commencing sulphonylureas or metformin between 1994 and 2002. In 2001-2002, metformin was more likely to be used in obese than non-obese patients: 13% normal weight, 33.6% overweight and 62.1% obese patients were treated with metformin. Glycaemic response to sulphonylureas was not influenced by BMI (P = 0.81). Metformin was more effective in lowering glucose in those with a lower BMI (r = -0.02, P = 0.02), although the clinical impact of this was small. The HbA(1c) reduction in non-obese patients was similar to that in obese patients (1.46% vs. 1.34%, P = 0.11). Glycaemic response to metformin in non-obese and obese patients is similar, suggesting that an individual's BMI should not influence the choice of oral agent. Given the non-glycaemia-related benefits of metformin, it should be used in more non-obese patients than is current practice in Tayside, Scotland.