Reditn M Adverse Reactions

Metabolic: Metformin-sitagliptin: Very common (10% or more): Hypoglycemia (13.8% when combined with sulfonylurea; 10.9% when combined with insulin).
Common (1% to 10%): Hypoglycemia, decrease levels of vitamin B12 without clinical manifestations and rarely associated with anemia.
Rare (less than 0.1%): Lactic acidosis due to metformin.
Sitagliptin: Uncommon (0.1% to 1%): Hypoglycemia.
Metformin: Common (1% to 10%): Hypoglycemia (5% or more when combined with glyburide).
Uncommon (0.1% to 1%): Hypoglycemia.
Very rare (less than 0.01%): Lactic acidosis, vitamin B12 deficiency.
In metformin-treated patients, the incidence of lactic acidosis has been about 1.5 cases per 10,000 patient years. The risk of lactic acidosis has been particularly high in patients with underlying renal insufficiency and rarely in patients with normal renal function. Concomitant cardiovascular or liver disease, sepsis, and hypoxia have also increased the risk of lactic acidosis.
Signs and symptoms of severe acidosis may include vomiting, abdominal pain, nausea, dyspnea, hypothermia, hypotension, and bradycardia.
Long-term treatment with metformin has been associated with a decrease in vitamin B12 absorption. Malabsorption of vitamin B12, due to intrinsic factor deficiency and possibly other mechanisms, in as many as 30% of treated patients, were reported. Megaloblastic anemia has occurred. Decreased levels of vitamin B12 appear to be reversible with discontinuation of metformin or vitamin B12 supplementation.
Gastrointestinal: Common (1% to 10%): Diarrhea, nausea, flatulence, vomiting.
Uncommon (0.1% to 1%): Constipation, upper abdominal pain, dry mouth.
Postmarketing reports: Indigestion, abdominal discomfort, dyspepsia, abdominal pain, acute pancreatitis (including fatal and non-fatal hemorrhagic and necrotizing pancreatitis), mouth ulceration, stomatitis.
Metformin: Very common (10% or more): Nausea, vomiting, diarrhea, abdominal pain, loss of appetite.
Sitagliptin: Rare (less than 0.1%): Pancreatitis.
Nervous system: Metformin-sitagliptin: Common (1% to 10%): Headache.
Uncommon (0.1% to 1%): Somnolence.
Frequency not reported: Asthenia.
Metformin: Common (1% to 10%): metallic taste.
Respiratory: Common (1% to 10%): Upper respiratory tract infections, nasopharyngitis, pharyngolaryngeal pain, bronchitis, sinusitis, influenza.
Postmarketing reports: Interstitial lung disease.
Hypersensitivity: Frequency not reported: Hypersensitivity reactions including anaphylaxis.
Hepatic: Metformin-sitagliptin: Postmarketing reports: Hepatic enzyme elevation.
Metformin: Very rare (less than 0.01%): Liver function disorders, hepatitis.
Renal: Frequency not reported: Impaired renal function, acute renal failure (sometimes requiring dialysis).
Musculoskeletal: Between October 2006 and December 2013, thirty-three cases of severe arthralgia have been reported to the FDA Adverse Event Reporting System Database. Each case involved the use of 1 or more dipeptidyl peptidase-4 (DPP-4) inhibitor. In all cases, substantial reduction in prior activity level was reported, 10 patients were hospitalized due to disabling joint pain. In 22 cases, symptoms appeared within 1 month of starting therapy, in 23 cases symptoms resolved less than 1 month after discontinuation. A positive rechallenge was reported in 8 cases, with 6 cases involving use of a different DPP-4 inhibitor. Sitagliptin had the greatest number of cases reported (n=28) followed by saxagliptin (n=5), linagliptin (n=2), alogliptin (n=1), and vildagliptin (n=2).
Common (1% to 10%): Arthralgia.
Postmarketing reports: Myalgia, pain in extremities, back pain, rhabdomyolysis.
General: Common (1% to 10%): Peripheral edema.
Dermatologic: Postmarketing reports: Angioedema, rash, urticaria, pruritus, cutaneous vasculitis, exfoliative skin conditions including Stevens-Johnson syndrome.
Metformin: Very rare (less than 0.01%): Urticaria, erythema, pruritus.
Hematologic: Decreased serum vitamin B12 levels, without clinical manifestations (rarely megaloblastic anemia), has been reported in approximately 7% of patients. The reduction in vitamin B12 levels may be due to interference with B12 absorption from the B12-intrinsic factor complex and appears to be rapidly reversible with discontinuation of metformin or vitamin B12 supplementation.
Rare (less than 0.1%): Megaloblastic anemia.