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Glimepiride / rosiglitazone Side Effects

For the Consumer

Applies to glimepiride / rosiglitazone: oral tablet

Along with its needed effects, glimepiride/rosiglitazone may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking glimepiride / rosiglitazone:

More common

Less common

  • Anxiety
  • blurred vision
  • chest pain or discomfort
  • cold sweats
  • coma
  • confusion
  • cool, pale skin
  • decreased urine output
  • depression
  • dilated neck veins
  • dizziness
  • extreme fatigue
  • fast heartbeat
  • increased hunger
  • irregular breathing
  • irregular heartbeat
  • nausea
  • nightmares
  • seizures
  • shakiness
  • slurred speech
  • swelling of the face, fingers, feet, or lower legs
  • tightness in the chest
  • troubled breathing with exertion
  • unusual bleeding or bruising
  • weight gain

Incidence not known

  • Abdominal or stomach pain or tenderness
  • agitation
  • back, leg, or stomach pains
  • bleeding gums
  • bloody, black, or tarry stools
  • blue lips and fingernails
  • coughing that sometimes produces a pink frothy sputum
  • dark urine
  • decreased appetite
  • difficult, fast, or noisy breathing
  • fluid-filled skin blisters
  • general body swelling
  • hostility
  • increased sweating
  • increased thirst
  • irritability
  • itching or skin rash
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • light-colored stools
  • loss of appetite
  • muscle pain or cramps
  • muscle twitching
  • nosebleeds
  • pain or discomfort in the arms, jaw, back, or neck
  • redness of the skin
  • seizures
  • sensitivity to the sun
  • skin thinness
  • sores, ulcers, or white spots on the lips or in the mouth
  • stupor
  • sweating
  • swollen glands
  • vomiting
  • yellow eyes or skin

Some side effects of glimepiride / rosiglitazone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

  • Lack or loss of strength


  • Burning, stinging, itching, or redness of the skin not present before treatment

Incidence not known

For Healthcare Professionals

Applies to glimepiride / rosiglitazone: oral tablet


Frequency not reported: Resumption of ovulation in premenopausal, anovulatory women, hormonal imbalance[Ref]


Major Adverse Cardiovascular Events:
Overall data from rosiglitazone long-term trials including the RECORD, ADOPT, and DREAM trials (rosiglitazone n=6311; control n=7756) showed no difference in overall mortality or major adverse cardiovascular events; however, a meta-analysis of shorter-term trials suggests and increased risk for myocardial infarction with rosiglitazone compared with placebo.

The RECORD trial (Rosiglitazone evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes; mean age 58 years; 52% male) revealed no significant difference in cardiovascular hospitalization or cardiovascular death (primary outcome) among patients with type 2 diabetes receiving rosiglitazone add-on therapy (n=2220) compared with active control (n=2227); however, there was a significant difference in the incidence of congestive heart failure (secondary endpoint). Patients who had failed metformin or sulfonylurea monotherapy were randomized to add-on rosiglitazone or active control (add-on metformin for those inadequately controlled on sulfonylurea or add-on sulfonylurea for those inadequately controlled on metformin). Patients were treated to a target glycosylated hemoglobin (HbA1c) of 7% or less. Heart failure was reported in 61 patients receiving add-on rosiglitazone and 29 patients receiving active control.

In a retrospective analysis of 42 clinical trials (mean duration 6 months), rosiglitazone was associated with an increased risk of myocardial ischemia compared with combined active or placebo control (2% versus 1.53%). These events included angina pectoris, angina dyspnea, myocardial infarction, coronary thrombosis, myocardial ischemia, coronary artery disease, and coronary artery disorder. There was an increased risk with combination insulin therapy and in patients receiving nitrates for known coronary heart disease.

Cardiovascular Events in Patients with NYHA Class I and II Heart Failure:
An increased risk of cardiovascular events was observed in a 52-week trial in patients with NYHA Class I and II Heart Failure receiving rosiglitazone (n=110) compared with placebo (n=114). These events included: cardiovascular deaths (5% vs 4%), worsening CHF (6% vs 4%), new or worsening edema (25% vs 9%), new or worsening dyspnea (26% vs 17%), increases in CHF medication (33% vs 18%), and cardiovascular hospitalization (19% vs 13%).

-Dose-related edema was reported in rosiglitazone clinical trials. In patients receiving rosiglitazone 8 mg in combination with a sulfonylurea, the incidence of edema was 12.4%. In monotherapy trials, edema was reported in 4.8% of patients receiving rosiglitazone (dose not specified). Healthy volunteers receiving rosiglitazone 8 mg once daily for 8 weeks experienced a statistically significant increase in median plasma volume compared with placebo.

Concomitant Administration with Insulin:
-Edema was reported with higher frequency in the rosiglitazone plus insulin combination trials (insulin, 5.4%; and rosiglitazone with insulin 14.7%). Reports of new onset or exacerbation of congestive heart failure occurred at a rate of 1% for insulin alone, 2% (4 mg) and 3% (8 mg) for insulin in combination with rosiglitazone. The coadministration of rosiglitazone and insulin is not recommended.[Ref]

Common (1% to 10%): Edema, hypertension
Uncommon (0.1% to 1%): Congestive heart failure

Glimepiride: Common (1% to 10%): Edema, hypertension

Common (1% to 10%): Edema, hypertension
Uncommon (0.1% to 1%): Congestive heart failure
Frequency not reported: Cardiovascular deaths, myocardial infarction, angina, angina pectoris, angina dyspnea, myocardial infarction, coronary thrombosis, myocardial ischemia, coronary artery disease, coronary artery disorder[Ref]


Common (1% to 10%): Nasopharyngitis

Common (1% to 10%): Upper respiratory infection
Postmarketing reports: Pulmonary edema, pleural effusions[Ref]

Nervous system

Common (1% to 10%): Headache, dizziness

Common (1% to 10%): Headache, dizziness

Common (1% to 10%): Headache
Frequency not reported: Stroke[Ref]


The most commonly reported adverse reports included headache, hypoglycemia, and nasopharyngitis.[Ref]


Common (1% to 10%): Nausea
Rare (less than 0.1%): Vomiting, gastrointestinal pain, diarrhea

Common (1% to 10%): Diarrhea[Ref]


Rare (less than 0.1%): Liver enzyme elevations,
Frequency not reported: Liver function impairment, e.g., cholestasis, jaundice, hepatitis, hepatic porphyria reactions and disulfiram-like reactions

Postmarketing reports: Hepatitis, hepatic enzyme elevations greater than 3 times the upper limit of normal, hepatic failure[Ref]


Postmarketing reports: Anaphylactic reaction[Ref]


Rare (less than 0.1%): Allergic skin reactions, e.g. pruritus, erythema, urticaria, and morbilliform or maculopapular eruptions
Frequency not reported: Porphyria cutanea tarda, photosensitivity reactions, allergic vasculitis

Postmarketing reports: Rash, pruritus, urticaria, angioedema, Stevens-Johnson syndrome[Ref]


Anemia was reported in 1.9% of patients receiving rosiglitazone as monotherapy. When taken in combination with metformin, a sulfonylurea, or metformin plus a sulfonylurea, the incidence of anemia was 7.1%, 2.3%, and 6.7%, respectively. Laboratory findings have shown dose-related decreases in hemoglobin and hematocrit; mean decreases in hemoglobin were 1 g/dL and up to 3.3% in hematocrit. These changes primarily occurred during the first 3 months or following a dose increase. They may be related to increased plasma volume.[Ref]

Frequency not reported: Leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia, pancytopenia

Common (1% to 10%): Anemia
Frequency not reported: Decrease in WBC counts[Ref]


Common (1% to 10%): Hypoglycemia
Frequency not reported: Weight gain

Common (1% to 10%): Hypoglycemia
Frequency not reported: Hyponatremia, syndrome of inappropriate antidiuretic hormone (SIADH) secretion, changes in serum lipids

Uncommon (0.1% to 1%): Hypoglycemia[Ref]

The mechanism of weight gain is unclear, although it probably is due to a combination of fluid retention and fat accumulation. Dose-related weight gain was observed in trials with the combination glimepiride / rosiglitazone and rosiglitazone alone. Mean weight gain in patients receiving the combination glimepiride 4 mg/rosiglitazone 4 mg was 2.2 kg and 2.9 kg for patients receiving glimepiride 4 mg/rosiglitazone 8 mg.[Ref]


Uncommon (0.1% to 1%): Blurred vision

Postmarketing reports: Diabetic macular edema with decreased visual acuity[Ref]


Common: Back pain, arthralgia,
Frequency not reported: Fractures, bone mineral density decreases[Ref]

Large long-term clinical trials have shown an increased incidence of bone fracture in patients receiving rosiglitazone in combination with sulfonylurea or metformin as rosiglitazone alone. This increased incidence appeared after the first year and persisted. The majority of fractures were observed in women and occurred in the upper arm, hand, and foot.[Ref]


Common (1% to 10%): Asthenia

Common (1% to 10%): Injury[Ref]


1. "Product Information. Avandaryl (glimepiride-rosiglitazone)." GlaxoSmithKline, Research Triangle Park, NC.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.