Metformin sulphonylureas combination

Olsson J, Lindberg G, Gottsater M, Lindwall K, Sjostrand A, Tisell A, Melander A. Increased mortality in Type II diabetic patients using sulphonylurea and metformin in combination a population-based observational study. Diabetologia 2000 43(5) 558-60. 

Rosiglitazone is a thiazolidinedione that can be used in combination with metformin or a sulphonylurea such as gliclazide. Rosiglitazone should be administered with caution in patients with cardiovascular disease. 

Sitagliptin is a dipeptidylpeptidase-4 inhibitor that increases insulin secretion and lowers glucagon secretion. Sitagliptin is available for oral administration. It is indicated in patients with type 2 diabetes mellitus in combination with either metformin (biguanide) or a sulphonylurea or a thiazolidinedione. 

Avandia (rosiglitazone) as with other thiazolidinediones is used either as monotherapy or in combination with either metformin or a sulphonylurea. A disadvantage of rosiglitazone is the risk of heart failure as a side-effect. This risk is increased when rosiglitazone is used in patients with cardiovascular disease and when used in combination with insulin. Blood-glucose control may deteriorate temporarily when a thiazolidinedione is substituted for an oral antidiabetic agent. 

Gulliford M, Latinovic R. Mortality in type 2 diabetic subjects prescribed metformin and sulphonylurea drugs in combination cohort study. Diabetes Metab Res Rev... 

Metformin (t) 5 h) is taken with or after meals. Its chief use is in the obese patient with Type 2 diabetes either alone or in combination with a sulphonylurea. It has a mild anorexic effect which helps to reduce weight in the obese. The action of metformin is terminated by excretion by the kidney and it should not be used in the presence of renal impairment. 

Insulin treatment in Type 2 diabetes. When oral therapy fails, insulin treatment should be used alone or in combination with metformin. There is little advantage from adding insulin to a sulphonylurea. The advent of thiazolidinediones offers an alternative to combining metformin with insulin, but more experience of these drugs is required before their combination with metformin can be routinely recommended. It is important to stop the thiazo-lidinedione, if not effective, before progressing to insulin. Definitive evidence that institution of insulin will reduce complications is lacking however, there is an improvement in quality of life, with few patients requesting to stop insulin once they have... 

There are three conditions for the clinical use of metformin as a glucose-lowering agent in patients with NIDDM (1) as a primary drug, (2) in combination with other oral hypoglycaemic agents such as sulphonylureas and acarbose, and (3) together with insulin after secondary sulphonylurea failure. 

For a review, see Sachse etal. (1982). Combining acarbose with sulphonylurea or metformin or insulin may lead to hypoglycaemia, although acarbose itself will not produce hypoglycaemia (doses have to be corrected). The effect of acarbose may be reduced by antacids, cholestyramine, pancreatic enzymes and adsorbants. Plasma levels of vitamin B6 increased, and vitamin A concentrations decreased with acarbose (Couet et al., 1989). 

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