Metformin Side Effects: Incidence Rates in Clinical Trials

Which reactions the labels list

The immediate-release metformin hydrochloride label's main table lists the reactions above 5% that were more common than placebo: diarrhea, nausea and vomiting, flatulence, asthenia, indigestion, abdominal discomfort and headache, and diarrhea led to discontinuation in 6% [1]. Its separate 1% to 5% list runs from abnormal stools and hypoglycemia through dyspnea, myalgia, rash, taste disorder, chest discomfort and palpitation [1].

The extended-release label reports diarrhea in 10% versus 3% on placebo and nausea and vomiting in 7% versus 2%, with diarrhea discontinuation in 0.6% [2]. Its 1% to 5% band covers abdominal pain, constipation, distention of the abdomen, dyspepsia and heartburn, flatulence, dizziness, headache, upper respiratory infection and taste disturbance [2]. The postmarketing sections of both labels cover cholestatic, hepatocellular and mixed hepatocellular liver injury [1][2].

Which breathing symptoms the label does mention

Dyspnea sits in the immediate-release 1% to 5% list, reported more often than with placebo [1]. Upper respiratory infection sits in the extended-release 1% to 5% list [2]. Respiratory distress appears in the boxed warning as one of the nonspecific symptoms that can accompany metformin-associated lactic acidosis, alongside malaise, myalgias, somnolence and abdominal pain; the warning describes the onset as often subtle [1][2].

Other documented effects

Diarrhea is the most frequent reaction in both labels. In 29-week immediate-release trials, previously normal blood vitamin B12 fell to subnormal levels in approximately 7% of patients, and the label directs measuring hematologic parameters annually and vitamin B12 every 2 to 3 years [1].

Metformin-associated lactic acidosis is a postmarketing event covered by a boxed warning rather than a trial incidence figure, and the label says cases primarily occurred in patients with significant renal impairment [1][2].