Metformin Acarbose

Thioctic acid is reported not to interact with acarbose, metformin or glibenciamide (giyburide). 

Other combination options Metformin or a Sulfonylurea plus Acarbose/Miglitol, or Pioglitazone/ Rosiglitazone or Repaglinide (with metformin), or Insulin... 

The addition of metformin to acarbose in 49 patients produced a synergistic effect (12). 

The effect of adding acarbose (maximum 100 mg tds) or placebo to insulin (20) or metformin (21) has been investigated in 1946 patients with type 2 diabetes. The results were comparable with the results of the UK Prospective Diabetes Study (22). After 3 years, 39% were still using acarbose compared with 58% using placebo. The main reasons for stopping were flatulence (30 versus 12%) or diarrhea (16 versus 8%). After 3 years the HbAic concentration was 0.5% lower (median 8.1 versus 8.6%). Acarbose was equally effective when added to diet, sulfonylurea, metformin, or insulin. 

In a multicenter, double-blind, placebo-controlled study, 81 patients, in whom treatment with metformin was inadequate, received extra acarbose or placebo during 24 weeks after a 4-week run-in period to establish the optimal dose of acarbose (28). HbAic was reduced by 1.02% and fasting blood glucose by 1.13 mmol/1. Gastrointestinal adverse effects were more common in the acarbose group. 

Acarbose reduces the absorption of metformin (79), as does miglitol (77). 

Hanefeld M, Bar K. Efficacy and safety of combined treatment of type 2 diabetes with acarbose and metformin. Diabetes Stoffwechsel 1998 7 186-90. 

Rosenstock J, Brown A, Fischer J, Jain A, Littlejohn T, Nadeau D, Sussman A, Taylor T, Krol A, Magner J. Efficacy and safety of acarbose in metformin-treated patients with type 2 diabetes. Diabetes Care 1998 21(12) 2050-5. 

Phillips P, Karrasch J, Scott R, Wilson D, Moses R. Acarbose improves glycemic control in overweight type 2 diabetic patients insufficiently treated with metformin. Diabetes Care 2003 26(2) 269-73. 

Metformin can be effectively combined with miglitol (SEDA-25, 514) but metformin may accumulate in the gastrointestinal wall, and the combination of metformin with acarbose or miglitol may reduce the absorption of metformin (136,137). 

A 54-year-old woman with gestational diabetes was later found to be allergic to chromium, pollen, dust, penicillin, acarbose, and metformin (130). She was treated with diet and glibenclamide, but later required insulin. With Humulin N insulin she developed a wheal of 15 mm immediately after the injection, which resolved in a few hours. However, a painful itchy induration appeared 2-3 hours after the injection and lasted a few days. She had an immediate reaction to isophane insulin, with induration, but insulin lispro was well-tolerated. 

A 38-year-old woman was given insulin when glibenclamide and acarbose failed. Troglitazone 400 mg/day was added and increased to 800 mg/day 1 month later. After 2 months her liver function tests were normal, but she developed jaundice after 4 months. Total and direct bilirubin were 127 and 101 pmol/l and alanine transaminase was 34 pkat/l. After withdrawal of troglitazone her symptoms disappeared and her liver function tests normalized within several months. Metformin 1000 mg bd reduced her insulin requirement. Rosiglitazone 4 mg bd was added and her liver function tests remained normal for 10 months. 

The effect of adding acarbose (maximum 100 mg tds) or placebo to insulin (15) or metformin (16) has been investigated in 1946 patients with type 2 diabetes. The results were comparable with the results of the UK Prospective... 

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. 

In conclusion, it can be stated, that biguanides, preferably metformin, have been shown in innumerable clinical trials to be highly effective as antihyper-glycaemic drugs. Together with acarbose, they may be the first-choice drug for the treatment of obese hyperinsulinaemic, insulin resistant Type-II diabetics with dietary failure. They help to correct most of the unwanted aspects of the metabolic syndrome, which is felt to contribute most to the high mortality rate of NIDDM patients with heart disease. 

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). 

The therapeutic effects of acarbose and biguanides have been compared in Type-II diabetics (Pagano and Cavallo-Perin, 1990) and found to be nearly equally effective. The same was true in studies (by Schwedes et al. (1982), who compared acarbose and metformin in poorly controlled NIDDM, while Schoffling et al. (1982) reported that acarbose was even more effective than metformin. Drost et al. (1982) concluded from their studies, however, that there was no basic difference between the hypoglycaemic effects of acarbose and metformin. Petersen (1982) tested the efficacy of acarbose versus buformin in NIDDM. Acarbose was found to reduce postprandial but not fasting blood glucose levels and to be slightly less effective than buformin. 

The oral antidiabetic drugs are the sulfonyiureas, metformin, acarbose, thiazolidinediones, and j repaglinide. 

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