Liraglutide 3 mg on weight, body composition, and hormonal and metabolic parameters in women with obesity and polycystic ovary syndrome: a randomized placebo-controlled-phase 3 study.

OBJECTIVE: To study the efficacy and safety of the GLP-1 analog liraglutide 3 mg (LIRA 3 mg) vs. placebo (PL) for reduction of body weight (BW) and hyperandrogenism in women with obesity and polycystic ovary syndrome (PCOS). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Hospital-based outpatient endocrine and metabolic center. PATIENT(S): Women diagnosed with PCOS (NIH criteria) were randomly assigned to LIRA 3 mg (n = 55) or PL (n = 27) once daily for 32 weeks with lifestyle intervention. INTERVENTION(S): Study visits at baseline and 32 weeks included BW and body composition by dual-energy x-ray absorptiometry. Oral glucose tolerance tests were done with sex steroids, free androgen index (FAI), and lipids measured in the fasting sample. MAIN OUTCOME MEASURE(S): The primary end points were changes in BW and FAI. Safety was assessed in all patients who received at least one dose of the study drug. RESULT(S): Change in BW from baseline to week 32 was -5.7% (±0.75) with LIRA 3 mg vs. -1.4% (±1.09) with PL. At week 32, more participants on LIRA 3 mg than on PL achieved at least 5% weight reductions (25 of 44 vs. 5 of 23). Free androgen index significantly reduced with LIRA 3 mg compared with the PL where the mean FAI slightly increased. Gastrointestinal events, which were mostly mild to moderate, were reported in 58.2% of the LIRA 3 mg-subjects and 18.5% of PL subjects. CONCLUSION(S): LIRA 3 mg once daily appears superior to PL in reducing BW and androgenicity and improving cardiometabolic parameters in women with PCOS and obesity. CLINICAL TRIAL REGISTRATION NUMBER: NCT03480022.

Exenatide, Dapagliflozin, or Phentermine/Topiramate Differentially Affect Metabolic Profiles in Polycystic Ovary Syndrome.

CONTEXT: Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors reduce weight and improve insulin sensitivity via different mechanisms. OBJECTIVE: The efficacy of once-weekly exenatide (EQW) and dapagliflozin (DAPA) alone and coadministered (EQW/DAPA), DAPA/extended-release (ER) metformin (DAPA/MET), and phentermine topiramate extended release (PHEN/TPM) on metabolic parameters, body composition, and sex hormones were examined in obese women with PCOS. METHODS: Nondiabetic women (n = 119; aged 18-45 years) with a body mass index (BMI) greater than 30 and less than 45 and polycystic ovary syndrome (National Institutes of Health criteria) were randomly assigned in a single-blinded fashion to EQW (2 mg weekly); DAPA (10 mg daily), EQW/DAPA (2 mg weekly/10 mg daily), DAPA (10 mg)/MET (2000 mg XR daily), or PHEN (7.5 mg)/TPM (46 mg ER daily) treatment for 24 weeks. Study visits at baseline and 24 weeks included weight, blood pressure (BP), waist (WC) measures, and body composition evaluated by dual-energy x-ray absorptiometry (DXA). Oral glucose tolerance tests were conducted to assess glycemia and mean blood glucose (MBG), and compute insulin sensitivity (SI) and secretion (IS) measures. Sex steroids, free androgen index (FAI), and lipid profiles were measured in the fasting sample. RESULTS: EQW/DAPA and PHEN/TPM resulted in the most loss of weight and total body fat by DXA, and WC. Despite equivalent reductions in BMI and WC with PHEN/TPM, only EQW/DAPA and EQW resulted in significant improvements in MBG, SI, and IS. Reductions in fasting glucose, testosterone, FAI, and BP were seen with all drugs. CONCLUSION: Dual therapy with EQW/DAPA was superior to either alone, DAPA/MET and PHEN/TPM in terms of clinical and metabolic benefits in this patient population.

Pregnancy rates from intrauterine insemination are equivalent following 1- versus 5-day letrozole administration for ovulation induction: a retrospective study.

OBJECTIVE: To compare the efficacy of single-dose letrozole (25 mg) with a 5-day course (5 mg/day) for ovulation induction (OI). DESIGN: Retrospective cohort study. SETTING: Hospital. PATIENTS: Patients undergoing first round of OI and intrauterine insemination with letrozole from January 2015 through December 2017. INTERVENTIONS: Patients received letrozole as either a single 25 mg dose for 1 day (1D) versus 5 mg daily for 5 days (5D). A secondary analysis was performed on patients also receiving gonadotropins (GND). MAIN OUTCOME MEASURES: Pregnancy rate (PR) determined by positive human chorionic GND. RESULTS: There were 847 patients included in the study, 302 in the 1D group and 284 in the 5D group; 261 patients had concurrent GND administration, 162 1D+GND and 99 5D+GND. There was no difference in smoking status, primary versus secondary infertility, or total motile sperm concentration. Comparing 1D with 5D, there was a statistically significant, although not clinically relevant, difference in both age and body mass index (31 vs. 31.8 years; 26.2 vs. 27.4, respectively). Similarly, comparing 1D+GND with 5D+GND, there was statistically significant difference in body mass index (27.19 vs. 29.1). Secondary outcomes included live birth rate (LBR), multiple gestation rate (MG), and miscarriage rate (SAB). There were no differences between 1D and 5D in the primary outcome of PR (14.2% vs. 11.6%), LBR (9.6% vs. 7%), MG (16.2% vs. 13.8%), or SAB (16.22% vs. 13.8%). In looking at the GND groups alone, there was no difference in PR (18.3% vs. 23.8%), LBR (11.72% vs. 17.86%), MG (8.7% vs. 5.56%), or SAB (13.64% vs. 5.56%). There was a significant difference in cycle cancellation rate in the 1D versus 5D groups (3.9% vs. 9.6%); however, this was not seen in the 1D+GND versus 5D+GND groups. CONCLUSIONS: A single-dose protocol with letrozole in an OI/intrauterine insemination cycle may be considered an alternative to standard 5D dosing protocols with the potential for improved compliance and similar reproductive outcomes.

Spontaneous reduction of multiple pregnancy: incidence and effect on outcome.

OBJECTIVE: Our objective was to determine the incidence of spontaneous reduction in multiple pregnancies during the first 12 gestational weeks and determine the outcome of the surviving fetuses. STUDY DESIGN: Analysis of prospectively collected ultrasound and birth information on 709 multiple and 5962 singleton pregnancies conceived at a private infertility clinic. RESULTS: Spontaneous reduction of one or more gestational sacs and or embryos occurred before the 12th week of gestation in 36% of twin (95% CI, 32%-40%), 53% of triplet (95% CI, 44%-61%), and 65% of quadruplet (95% CI, 46%-85%) pregnancies. Reduction was less frequent after ovulation induction than after spontaneous ovulation. In general, pregnancy duration and birth weight were inversely related to the initial gestational sac number irrespective of the final birth number. CONCLUSIONS: More than 50% of patients with 3 or more gestational sacs had spontaneous reduction before 12 weeks. The surviving fetuses weighed less and were born earlier than unreduced pregnancies with the same initial number of fetuses.