Orforglipron

How a course is commonly described

1. 1
   Days 1-30: 0.8 mgClinical

   The label starts everyone at 0.8 mg once daily, held for at least 30 days, explicitly to limit gastrointestinal reactions. Tablets are swallowed whole at any time of day, with or without food, and no more than one tablet is taken per day.

2. 2
   Days 31-90: 2.5 mg, then 5.5 mgCommunity-reported

   Two further steps follow, each after at least 30 days, bringing the patient to 5.5 mg by around month three. Community guides treat 5.5 mg as a decision point: stay there if the response is adequate, or keep stepping if not.

3. 3
   Month 4 onward: 9, 14.5 or 17.2 mgClinical

   Each additional step requires at least 30 days at the current dosage and is conditional on response and tolerability, with 17.2 mg the ceiling. The maximum drops to 9 mg if a strong CYP3A4 inhibitor is taken alongside.

4. 4
   Weeks 4-40: when change showsCommunity-reported

   Community guides place appetite changes in the first 2-4 weeks, visible weight change from weeks 4-8, and most of the loss accumulating between weeks 12 and 40 as the dose climbs. Trials measured their primary endpoint much later, at 40 weeks for the diabetes programme and 72 weeks for obesity.

5. 5
   Handling a missed dose or a hard stepCommunity-reported

   The label says to take a missed dose as soon as possible without doubling up, and to restart escalation at a lower dosage if 7 or more consecutive doses are missed. Community practice for a badly tolerated step is to drop back one level for an extra four weeks and retry.

6. 6
   Trial maintenance for comparisonClinical

   ATTAIN-1 ran maintenance at 6, 12 or 36 mg capsule doses to week 72, producing mean weight reductions of 7.5%, 8.4% and 11.2% against 2.1% on placebo. Those capsule figures are not the tablet strengths on the label, which run 0.8 to 17.2 mg for equivalent exposure.

• Trial papers and the approved label use two different dose scales: phase 3 reports describe capsules of 1 to 36 mg, while the marketed tablets are 0.8 to 17.2 mg for equivalent exposure. A 36 mg trial dose and a 17.2 mg tablet are the same exposure, not a reduction.
• Gastrointestinal effects dominate the safety record in every trial and cluster during escalation, which is why the label fixes a minimum of 30 days per step and why missing a week of doses means restarting lower. Discontinuation for adverse events ran 5-10% across the obesity trials and up to 20% in a diabetes comparison against dapagliflozin.
• The drug is approved only for long-term weight management in the United States; diabetes submissions are still under review, and trials in sleep apnoea, hypertension, osteoarthritis pain and peripheral arterial disease are ongoing. It carries a boxed warning for thyroid C-cell tumours and is contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2. The rows above record what sources report, not endorsements of use.