Biguanides diabetes

Three classes of oral therapeutic agent are available for treating patients with diabetes mellitiis (NIDDM) the arylsulfonylureas (known simply as sulfonylureas), biguanides, and a-glycosidase inhibitors. Since 1977, only the sulfonylureas have been approved for use in the United States, although the other classes are used elsewhere. 

The answer is a. (Hardman, p 1510.) Although the mechanism of action of metformin and other biguanicies is unclear, biguanides virtually never cause hypoglycemia They operate independently of pancreatic p cells but are not useful in insulin-dependent diabetes mellitus (IDDM). Some possible mechanisms of action are direct stimulation of glycolysis in peripheral tissues, increased sensitivity to insulin, and reduction of glucagon levels. 

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. 

Metformin is a biguanide used to treat diabetes mellitus. It is contraindicated in patients undergoing general anaesthesia since anaesthesia can interfere with renal function. The risk of lactic acidosis associated with metformin increases in patients with renal impairment. Metformin should be stopped before and during surgery where anaesthesia is indicated. Metformin should only be restarted after the renal function has returned to normal. 

Biguanides can be agents of first choice only in Type II diabetic patients with serious overweight as in these patients insulin resistance has a high prevalence. 

In patients with Type II diabetes the sulfonylureas can provide good control of blood glucose, but it remains controversial to what extend they are of benefit for the long-term prognosis and if they protect against tissue damage, e.g. microvasculopathy. Sometimes the combination of a sulfonylureas with a biguanide is indicated for adequate control. 

Bedtime insulin has been suggested as an adjunct to oral antidiabetic therapy in patients with type 2 diabetes who have not responded to maximal oral therapy. Clinical practice has evolved to include sulfonylureas, meglitinides, D-phenylalanine derivatives, biguanides, thiazolidinediones, or rr.-glucosidase inhibitors given in conjunction with insulin. 

Insulin secretagogues (sulfonylureas, meglitinides, or D -phenylalanine derivatives), Tzds, biguanides, -glucosidase inhibitors, and incretin-based agents are not approved for use in type 1 diabetes. 

In reaction to a report of lactic acidosis at a therapeutic metformin concentration (SEDA-22, 476), in which a mitochondrial defect was supposed to have increased susceptibility to metformin, it has been observed that diabetes itself may dispose to hyperlactatemia (71). Others (72) have taken issue with the opinion (SEDA-22, 476) that the association of lactic acidosis with metformin may be coincidental, as lactic acidosis can also emerge during critical illnesses (type A lactic acidosis, caused by circulatory insufficiency). However, patients with type B lactic acidosis, with high biguanide concentrations, will also develop circulatory insufficiency after some hours. 

Metformin can cause reduced vitamin Bi2 absorption, reducing serum Bi2 concentrations and causing megaloblastic anemia (87), the prevalence of which was 9% in 600 patients with type 2 diabetes taking biguanides (phen-formin or metformin) for a mean of 12 years (88). In 353 patients with type 2 diabetes, treated with insulin, who took metformin for 16 weeks in a placebo-controlled study, metformin increased serum homocysteine concentrations by 4% and reduced serum folate by 7% and vitamin Bi2 by 14% (89). 

Filioussi K, Bonovas S, Katsaros T. Should we screen diabetic patients using biguanides for megaloblastic anaemia Aust Fam Physician 2003 32 383 1. 

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