Metformin Cough: FDA Data Shows 2.25% Incidence Rate

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].

Why a 2.25% figure cannot come from adverse event reports

Spontaneous reports cannot supply an incidence rate. The FDA states that the information in its adverse event reports cannot be used to estimate the occurrence rates of the events reported, and that a report does not establish that the drug caused the event [3]. Duplicate and incomplete reports sit in the system, and the information in them has not been verified [3].

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].