Metformin diarrhea with

Primary side effects associated with metformin therapy are gastrointestinal in nature, including decreased appetite, nausea, and diarrhea. These side effects can be minimized through slow titration of the dose and often subside within 2 weeks. Discontinuation because of side effects occurs in only 3% to 5% of patients. 

Metformin, a biguanide derivative, can lower excessive blood glucose levels, provided that insulin is present Metformin does not stimulate insulin release. Glucose release from the liver is decreased, while peripheral uptake is enhanced. The danger of hypoglycemia apparently is not increased. Frequent adverse effects include anorexia, nausea, and diarrhea Overproduction of lactic acid (lactate acidosis, lethality 50%) is a rare, potentially fatal reactioa Metformin is used in combination with sulfony-lureas or by itself. It is contraindicated in renal insufficiency and should therefore be avoided in elderly patients. 

Adverse gastrointestinal symptoms (nausea, vomiting, anorexia, metallic taste, abdominal discomfort, and diarrhea) occur in up to 20% of individuals taking metformin this can be minimized by starting at a low dose and slowly titrating the dose upward with food. Like phenformin, metformin can cause lactic acidosis, but its occurrence is rare except when renal failure, hypoxemia, or severe congestive heart failure is present or when coadministered with alcohol. Metformin is also contraindicated in persons with hepatic dysfunction, but it appears to be safe for use in the hepatic steatosis that often occurs with fatty infiltration of the liver in poorly controlled type II diabetics. 

The most common toxic effects of metformin are gastrointestinal (anorexia, nausea, vomiting, abdominal discomfort, and diarrhea), which occur in up to 20% of patients. They are dose-related, tend to occur at the onset of therapy, and are often transient. However, metformin may have to be discontinued in 3-5% of patients because of persistent diarrhea. Absorption of vitamin B12 appears to be reduced during long-term metformin therapy, and annual screening of serum vitamin B12 levels and red blood cell parameters has been encouraged by the manufacturer to determine the need for vitamin B12 injections. In the absence of hypoxia or renal or hepatic insufficiency, lactic acidosis is less common with metformin therapy than with phenformin therapy. 

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 82 children aged 10-16 years with type 2 diabetes, metformin lowered HbAic and fasting blood glucose compared with placebo (12). More patients who took placebo had to drop out because more medication was necessary. Most of the adverse events (abdominal pain, diarrhea, nausea, vomiting) occurred during metformin treatment. 

In 43 patients with poorly controlled type 2 diabetes using insulin, the addition of metformin improved HbAic and reduced the dose of insulin (97). Seven patients in the metformin group and four in the placebo group had nausea nine versus four had diarrhea. 

Three patients who had taken metformin for more than 2 years developed diarrhea (98). After withdrawal of metformin the diarrhea resolved within 1 month. A fourth patient developed diarrhea after taking metformin for 4 months, which stopped after withdrawal rechallenge with metformin 8 months later led to recurrence. Three of these patients had bowel disease (diverticulosis, irritable bowel syndrome, and diabetic neuropathy). 

Adverse effects are more likely to occur with metformin at the start of therapy. In retrospective case note review comparison of modified-release and immediate-release metformin 9.2% of those newly started on modified-release metformin (n — 65) had gastrointestinal adverse effects compared with 20% of those who started on immediate-release metformin (n — 363) (126). The main gastrointestinal adverse effect was diarrhea. The mean doses were 1258 mg/day for modified-release metformin and 1282 mg/day for immediate-release metformin. 

A 59-year-old obese woman with normal renal function, taking metformin 500 mg tds, took orlistat 120 mg tds for 3 months (147). She developed abdominal pain and diarrhea, for which she was given cimetidine, and became weak and dizzy, with blurred vision, reduced consciousness, agitation, and confusion. Her pH was 6.5, bicarbonate 2 mmol/1, base deficit 38 mmol/1, and lactate 21 mmol/1. She required rehydration, bicarbonate, inotropic support and renal replacement therapy. 

Abdominal discomfort is frequent with metformin (15-25%), and nausea, vomiting, and diarrhea occur even in the absence of lactic acidosis. Other effects include flatulence, abdominal bloating, anorexia, and a metallic taste. Anorexia and weight loss are often seen at the beginning of treatment. Phenformin can cause hemorrhagic gastritis (65). 

Acute side effects of metformin, which occur in up to 20% of patients, include diarrhea, abdominal discomfort, nausea, metallic taste, and anorexia. These usually can be minimized by increasing the dosage of the drug slowly and taking it with meals. Intestinal absorption of vitamin B12 and folate often is decreased during chronic metformin therapy, and calcium supplements reverse the effect of metformin on vitamin B12 absorption. 

A 59-year-old woman with type 2 diabetes mellitus and coronary artery disease, taking fenofibrate, hsinopril, metformin, fluvastatin, and atenolol, was given cimetidine for gastroesophageal reflux disease and immediately developed nausea and vomiting followed by diarrhea. She had low hemoglobin, carbon... 

A 49-year-old woman who was taking metformin, losartan, bendroflumethiazide, and atenolol, developed diarrhea and vomiting after general anesthesia for a minor procedure [39 ]. Her symptoms continued for 5 days and worsened with the development of dyspnea. Her pH was less than 6.8 and the serum creatinine concentration was 769 p,mohl. She was treated with continuous hemofiltration for 4 days and made a good recovery. 

A six-month, open-label randomised study without placebo group in women with polycystic ovarian syndrome receiving metformin 1000 mg daily was conducted in 66 patients. The most common adverse event reported for metformin was vomiting n = 1), nausea (n = 3), diarrhea (n = 9). [24 ]... 

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