A Risk-Benefit Assessment of Metformin in Type 2 Diabetes Mellitus

Abstract

Metformin has been used for over 40 years as an effective glucose-lowering agent in type 2 (noninsulin-dependent) diabetes mellitus. Typically it reduces basal and postprandial hyperglycaemia by about 25% in more than 90% of patients when either given alone or coadministered with other therapies including insulin during a programme of managed care. Metformin counters insulin resistance and offers benefits against many features of the insulin resistance syndrome (Syndrome X) by preventing bodyweight gain, reducing hyperinsulinaemia and improving the lipid profile. In contrast to sulphonylureas, metformin does not increase insulin secretion or cause serious hypoglycaemia. Treatment of type 2 diabetes mellitus with metformin from diagnosis also offers greater protection against the chronic vascular complications of type 2 diabetes mellitus. The most serious complication associated with metformin is lactic acidosis which has an incidence of about 0.03 cases per 1000 patients years of treatment and a mortality risk of about 0.015 per 1000 patient-years. Most cases occur in patients who are wrongly prescribed the drug, particularly patients with impaired renal function (e.g. serum creatinine level > 130 micromol/L or > 1.5 g/L). Other major contraindications include congestive heart failure, hypoxic states and advanced liver disease. Serious adverse events with metformin are predictable rather than spontaneous and are potentially preventable if the prescribing guidelines are respected. Gastrointestinal adverse effects, notably diarrhoea, occur in less than 20% of patients and remit when the dosage is reduced. The life-threatening risks associated with metformin are rare and could mostly be avoided by strict adherence to the prescribing guidelines. Given the 4 decades of clinical experience with metformin, its antihyperglycaemic efficacy and benefits against Syndrome X, metformin offers a very favourable risk-benefit assessment when compared with the chronic morbidity and premature mortality among patients with type 2 diabetes mellitus.

Mechanisms and factors associated with gastrointestinal symptoms in patients with diabetes mellitus

“…Destaca-se a metformina, do grupo das biguanidas, e as sulfonilureias. Os sintomas mais frequentemente encontrados com o uso dessas medicações são diarreia e vômitos, os quais levam a uma piora na qualidade de vida dos pacientes com DMT2 e pode resultar em não aderência ao tratamento da doença 15,[58][59][60] .…”

Contraindications can damage your health—is metformin a case in point?

“…The first is that some patients do not tolerate it well, and the second is that traditional contraindications limit its use [5][6][7][8][9]. Although such contraindications are frequently overlooked in clinical practice, an increased incidence of serious side-effectsparticularly lactic acidosis-has not been observed [10][11][12][13][14].…”

“…However, while phenformin increases lactate turnover and suppresses lactate oxidation [19], with metformin the lactate that cannot be metabolised via gluconeogenesis can still be eliminated by a compensatory increase in lactate oxidation [15]. Table 1 shows the contraindications of metformin as given by manufacturers [5], British guidelines [6,7], the German Diabetes Association [8] and experts [9]. These are not perfectly congruent (creatinine clearance <60 ml/min in the package insert [5] vs <90 ml/min as an expert statement [9], or a serum creatinine of >106 μmol/l in a German guideline [8] vs 133 mg/dl in British guidelines [6,7]) and are sometimes not well defined (e.g.…”

“…Table 1 shows the contraindications of metformin as given by manufacturers [5], British guidelines [6,7], the German Diabetes Association [8] and experts [9]. These are not perfectly congruent (creatinine clearance <60 ml/min in the package insert [5] vs <90 ml/min as an expert statement [9], or a serum creatinine of >106 μmol/l in a German guideline [8] vs 133 mg/dl in British guidelines [6,7]) and are sometimes not well defined (e.g. advanced age).…”

The Current Scenario of Vitamin B12 Deficiency by Long Term Metformin Therapy in Diabetes Mellitus - Type 2 Patients

“…A case report of Metformin-associated lactic acidosis, in a patient on Peritoneal Dialysis was reviewed in a former study and the modes of treatment to treat this complication were established. [12][13][14][15][16][17][18][19] …”