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4.3 Comparative Safety with Newer Agents While Metformins safety profile is well-established, newer agents present different safety considerations

discuss with doctor if severe Week 1316: Maintenance Dose (9mg or continuing to 12mg) For 9mg group (maintenance): Side effects stabilize Nausea decreases (2025% still experiencing) Dysesthesia: 8.8% incidence (mild) Body adapting well For 12mg group (final increase): GI effects may temporarily worsen (4045% nausea) Dysesthesia peaks (20.9% incidence) This is the "make or break" dose highest efficacy, highest side effects Duration: 12 weeks adjustment period Week 17+: Long-Term Maintenance Side effects: Nausea: Decreases to 1525% (down from 4045%) Diarrhea: Improves to 1020% Dysesthesia: Stable at 8.820.9% (doesn't worsen) Most people feel "normal" except for reduced appetite Key point: Side effects are WORST during dose escalation (weeks 116)

1996 Feb;148(2):197-205