Treatment to Regress to Normoglycemia in Women with a Recent History of GDM (SWEET)

A Randomized, Placebo-controlled, Double Blind Trial of Semaglutide 1mg (Ozempic®) on Regression to Normoglycemia in WomEn with a Recent History of Gestational DiabETes Mellitus: the SWEET Study

The purpose of the study is to determine the efficacy of semaglutide 1mg (Ozempic®) to aid recently postpartum women with dysglycemia and a history of GDM to regress to normoglycemia; thereby filling a gap in efficacious pharmacologic intervention options for clinicians to support postpartum diabetes recovery and reduce future risk of T2DM in young women.

Study Overview

• Status: Recruiting
• Conditions: Pre Diabetes; Postpartum Disorder
• Intervention / Treatment: Drug: Semaglutide Pen Injector [Ozempic]; Drug: Placebo semaglutide pen injector

Detailed Description

The diagnosis of gestational diabetes mellitus (GDM) during pregnancy identifies young women with abnormalities in pancreatic beta cell function that worsen over time, leading to diabetes. It is estimated that between 15% and 70% of women with a history GDM will progress to type 2 diabetes mellitus (T2DM). However, upon an impaired glucose tolerance test result in the early postpartum period, the American College of Obstetricians and Gynecologists only recommend considering referral for management, weight loss and physical activity counseling, considering metformin if testing results are severe enough, and yearly assessment of glycemic status. In many cases, it is possible to reverse diabetes by losing weight in the early stages before permanent, systemic damage occurs. Therefore, there is a dire need for efficacious pharmacologic intervention options in this period of postpartum diabetes recovery to return women to normoglycemia and lower future T2DM risk. Weight loss and medications that mitigate impairments in insulin secretion show the best promise for delaying or preventing T2DM, the dominant form of diabetes that develops after GDM. The primary study objective is "to examine the efficacy of semaglutide 1mg compared to placebo on regression to normoglycemia in women with dysglycemia and a recent history of gestational diabetes mellitus (i.e., 6-36 months postpartum)" to answer the research question of: "Among women with dysglycemia and a recent history of gestational diabetes mellitus, can acute treatment of semaglutide 1mg lead to regression to normoglycemia?"

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Elizabeth Sutton, PhD; Phone Number: 225-924-8446; Email: elizabeth.sutton@womans.org
• Study Contact Backup: Name: Briasha Jones, MPH; Phone Number: 225-924-8446; Email: briasha.jones@womans.org

Study Locations

• United States
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70817
      • Recruiting
      • Woman's Hospital
      • Contact: Elizabeth Sutton, PhD; Phone Number: 225-924-8446; Email: elizabeth.sutton@womans.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Female
2. 18 - 45 years old (inclusive)
3. History of gestational diabetes in most recent pregnancy
4. 6 months - 10 years postpartum
5. BMI ≥ 25 kg/m2
6. Use of long-acting reversible contraception or bilateral tubal ligation

7. Dysglycemia as determined by glycemic response to 75g, 2-hour OGTT: either impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both (IFG/IGT):

   1. Fasting glucose 100-125mg/dL (inclusive) and/or
   2. 120 minute glucose 140-199mg/dL (inclusive)
8. Willingness to maintain physical activity level throughout study duration
9. Willingness to standardize diet for 3 days prior to OGTT
10. Ability to provide informed consent before any trial-related activities

Exclusion Criteria:

1. Body weight > 350lb
2. Pregnant or the intention of becoming pregnant or not using adequate contraceptive measures.
3. Breastfeeding within 3 months of screening visit 1
4. Post-menopausal
5. Desiring pregnancy within study participation period or two months after participation ends (i.e. 10 months from enrolment)
6. Use of tobacco products within past 6 months
7. Substance or alcohol abuse
8. Presence of significant systemic disease including: diabetes mellitus (type 1 or type 2), cardiac disease (e.g. congestive heart failure), renal impairment (e.g. serum creatinine levels ≥ 1.4 mg/dL or eGFR < 60), hepatic disease (including viral hepatitis, toxic hepatic damage, jaundice of unknown aetiology, or abnormal liver function tests), pancreatitis, uncontrolled thyroid disease (e.g. documented abnormal TSH), adrenal disease (including Cushing's syndrome, congenital adrenal hyperplasia), hyperlipidemia (fasting triglycerides > 399mg%), untreated or poorly controlled hypertension (resting blood pressure >159/94 mmHg)
9. History of or presence of: eating disorder, malignant disease requiring chemotherapy, or debilitating psychiatric disorder such as psychosis or neurological condition that could confound outcome variables
10. History of bariatric surgery
11. Use of medications for glucose regulation: insulin (e.g. Humalog, Novolog, Humulin), pramlintide, metiglinides, metformin, thiazolidinediones, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT2 inhibitors within four weeks of screening visit 1
12. Use of medications for anti-obesity or weight loss within four weeks of screening visit 1
13. Use of medications known to exacerbate glucose dysfunction (such as isotretinoin or corticosteroids) within four weeks of screening visit 1
14. Known or suspected allergy to trial medication, excipients, or related products
15. Contraindications to study medications: patients with a personal or family history of medullary thyroid cancer or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
16. Current or recent past (within 3 months) participation in another experimental drug trial
17. Previous randomization in this trial
18. Receipt of any investigational drug within 6 months prior to this trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Semaglutide Pen Injector (Ozempic); Weekly injections of semaglutide for 8 months total (2 months of titration; 6 months of full dose- 1mg/week)	Drug: Semaglutide Pen Injector [Ozempic]; Start injection of semaglutide 0.25mg subcutaneously (SC) once a week for 4 weeks; step up to 0.5 mg SC QD for once a week for 4 weeks to a final dose of 1.0 mg semaglutide SQ weekly for 24 doses; Other Names: Ozempic; Semaglutide 1mg
Sham Comparator: Placebo; Weekly injections of placebo for 8 months total	Drug: Placebo semaglutide pen injector; Start injection of placebo semaglutide 0.25mg subcutaneously (SC) one a week for 4 weeks; step up to 0.5 mg SC QD for once a week for 4 weeks to a final dose of 1.0 mg semaglutide SQ weekly for 24 doses; Other Names: Placebo Semaglutide 1mg; Placebo Ozempic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regression to normoglycemia	Glucose tolerance to be determined by glycemic response to a 75 gram, two-hour oral glucose tolerance test (OGTT). Regression to normoglycemia is defined by fasting glucose <100mg/dL and 120 minute glucose <140 mg/dL	After 24 weeks of full-dose treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c	Hemoglobin to be determined	After 24 weeks of full-dose treatment
Change in body weight	Fasted body weight after intervention minus fasted body weight at enrollment	After 24 weeks of full-dose treatment

Collaborators and Investigators

• Sponsor: Woman's
• Collaborators: Novo Nordisk A/S
• Investigators: Principal Investigator: Elizabeth Sutton, PhD, Woman's Hospital, Louisiana

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2022
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: April 29, 2021
• First Submitted That Met QC Criteria: April 29, 2021
• First Posted (Actual): May 5, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Pregnancy Complications; Glucose Metabolism Disorders; Diabetes Mellitus; Prediabetic State; Puerperal Disorders; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; Semaglutide
• Other Study ID Numbers: RP-21-010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No