Abstract

Abstract Disclosure: A. Arunachalam: None. A. Nguyen: None. N.L. Shah: None. Obesity is a global health challenge which can lead to type 2 diabetes, hypertension, cardiovascular disease, and decreased life expectancy. In addition to lifestyle intervention, pharmacotherapy to sustain weight loss has remained limited due to effectiveness, cost, and adverse effects. Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like-peptide-1 receptor agonist currently approved for type 2 diabetes treatment. Tirzepatide-induced weight loss may provide new options for treatment of obesity. We report a 32-year-old female with a history of T2DM and PCOS originally on metformin who was started on semaglutide 0.25 mg, which was uptitrated to 0.5mg weekly for 6 months. She lost 25 lbs with no side effects. Semaglutide and OCPs were discontinued due to fertility with her weight and hemoglobin A1C rebounding off medication. She was started on tirzepatide 2.5mg weekly. At that time, she weighed 223 lbs with a hemoglobin A1C 8.2%. She was counseled to resume OCPs and improve glucose control and weight reduction prior to attempting to conceive. Once increased tirzepatide dosing to 5mg weekly, she endorsed severe nausea and intermittent epigastric abdominal pain on day of injection. She attempted to increase dose to 7.5mg weekly, but dose was reduced due to complaints of constipation and worsened abdominal pain requiring bowel regimen. She remained on tirzepatide for a total of 4 months prior to becoming pregnant while on oral contraceptives. Her weight decreased from 223 to 212 lbs with reduction in hemoglobin A1C from 8.2% to 6.1%. While initially studied for use in type 2 diabetes, tirzepatide was found to induce clinically significant weight reduction. The recent SURMOUNT-1 trial, which studied the effects of tirzepatide in non-diabetics, demonstrated that once-weekly tirzepatide at three different doses demonstrated substantial and sustained weight reduction in patients with obesity. In trials involving patients with once-weekly injectable semaglutide, the mean reduction in hemoglobin A1C was 1.8 percentage points and reduction in mean body weight was 6.5 kg. In the SURPASS-2 trial, reductions in body weight were greater with tirzepatide when compared to semaglutide with mean estimated treatment difference −1.9kg, -3.6kg, and -5.5 kg respectively based on dosing of 5mg, 10mg, and 15mg. The adverse events most commonly reported in patients on tirzepatide include nausea, vomiting, and diarrhea, which occurred most commonly during dose-escalation. Mounjaro is known to reduce the efficacy of oral contraceptive pills due to delayed gastric emptying. This delay is largest after the first dose so recommended to switch from oral to non-oral contraceptives for the first four weeks when tirzepatide is initiated. It is important to counsel patients on the decreased efficacy of oral contraceptives while on tirzepatide. <!--EndFragment--> Presentation: Thursday, June 15, 2023

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