PSHP 2026 Residency Conference

Purpose: 
This retrospective cohort study characterized approaches for resuming semaglutide or tirzepatide after at least two consecutive missed doses and evaluated tolerability in outpatient clinics at Penn Presbyterian Medical Center (PPMC).


Methods: 
This study included adults who missed at least two consecutive doses of semaglutide or tirzepatide between October 2024 and November 2025 and reinitiated therapy at a non-starting dose. Exclusion criteria included patients who resumed at the lowest dose, those switching medications (except brand substitutions), or without follow-up data. Chart review captured demographics, indication, therapy duration before lapse, prior and resumed doses, and number of missed doses. The primary outcome was the tolerability associated with the dose step changes related to missed doses. Tolerability was defined as no patient-reported adverse drug reactions (ADRs), a dose increase or continuation. Intolerance was defined as any patient-reported ADR, a dose reduction, or discontinuation. Secondary outcomes included reasons for lapse and months saved by avoiding restart at the initial dose. Descriptive statistics were used.


Results:
Among 65 patients, the mean age was 46 years and 76.9% were female. Most were prescribed tirzepatide (46.2%) or semaglutide (38.5%) for weight loss. The median number of missed doses was 3 (IQR, 2 to 4), with a median dose step change of -1 (IQR, -2 to 0). A dose reduction occurred in 37 patients (57%), 24 patients (36.9%) had no change, and 4 patients (6.2%) had a dose increase. Overall, 95.4% of patients tolerated reinitiation. Access-related issues accounted for 87.7% of lapses. The median months saved by avoiding restart at the initial dose was 2 (IQR, 1 to 3). Additionally, tolerability remained high across missed-dose subgroups.


Conclusion: 
Resuming semaglutide or tirzepatide at a non-starting dose after at least two missed doses was well-tolerated in most patients. Dose reductions were common with high rates of tolerability. This approach prevented titration delays typically caused by missed doses. Further studies should prospectively evaluate optimal reinitiation strategies, including the impact on long-term weight loss and glycemic control.