In 0.7% of patients treated with GLUMETZA + SU, diarrhea was responsible for discontinuation of study medication compared to zero in the placebo + SU group.

In the same study, the following adverse events were reported by 1-5% of patients for the combined Glumetza + SU group and these events occurred more commonly in the Glumetza-treated than in the placebo-treated patients:

Ear and labyrinth disorders: ear pain

Gastrointestinal disorders: vomiting NOS, dyspepsia, flatulence, abdominal pain upper, abdominal distension, abdominal pain NOS, toothache, loose stools

General disorders and administration site conditions: asthenia, chest pain

Immune system disorders: seasonal allergy

Infections and infestations: gastroenteritis viral NOS, tooth abscess, tonsillitis, fungal infection NOS

Injury, poisoning and procedural complications: muscle strain

Musculoskeletal and connective tissue disorders: pain in limb, myalgia, muscle cramp

Nervous system disorders: dizziness, tremor, sinus headache, hypoaesthesia

Respiratory, thoracic and mediastinal disorders: nasal congestion

Skin and subcutaneous tissue disorders: contusion

Vascular disorders: hypertension NOS

No cases of overdose were reported during GLUMETZA clinical trials. It would be expected that adverse reactions of a more intense character including epigastric discomfort, nausea, and vomiting followed by diarrhea, drowsiness, weakness, dizziness, malaise and headache might be seen. Should those symptoms persist, lactic acidosis should be excluded. The drug should be discontinued and proper supportive therapy instituted. In other metformin clinical trials, hypoglycemia has not been seen even with ingestion of up to 85 grams of metformin, although lactic acidosis has occurred in such circumstances (see  WARNINGS ). Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected.

Table 5: Treatment-Emergent Adverse Events Reported By >5%* of Patients for the Combined Glumetza Group Versus Placebo Group  Adverse Event
(MedDRA Preferred Term)  Glumetza + SU
(n = 431)  Placebo + SU
(n = 144) 
Hypoglycemia NOS  13.7%  4.9% 
Diarrhea  12.5%  5.6% 
Nausea  6.7%  4.2% 

GLUMETZA should be taken once daily. However, there is no fixed dosage regimen for the management of hyperglycemia in patients with type 2 diabetes with GLUMETZA or any other pharmacologic agent. Dosage of GLUMETZA must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily dose. The maximum recommended daily dose of GLUMETZA is 2000 mg. GLUMETZA therapy should generally be initiated with 1000 mg daily which should be taken with food preferably in the evening. Gradual dose escalation from this low dose is recommended both to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control. During treatment initiation and dose titration (see  Recommended Dosing Schedule ), fasting plasma glucose shoul