Clinical trial NCT06948825: Effectiveness Study of a Lifestyle Intervention Versus Metformin in Mothers With Recent Gestational Diabetes
Official title: Effectiveness Study of a Lifestyle Intervention Versus Metformin in Mothers With Recent Gestational Diabetes
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Weight Loss
Gestational Diabetes Mellitus in Pregnancy
Postpartum Care
Keywords: diabetes prevention
gestational diabetes
lifestyle intervention
Lead sponsor: George Washington University
Sponsor class: OTHER
Collaborators: name: University of North Carolina
name: Diabetes Sisters
name: American Diabetes Association
First posted: 2025-04-29
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Adaptive trial design. All participants receive the basic lifestyle intervention. If they do not reach their weight loss threshold, they are then randomized to an enhanced lifestyle intervention or Metformin.
Primary purpose: PREVENTION

Brief summary: The goal of this clinical trial is to evaluate the effectiveness of a 6-month lifestyle intervention compared to Metformin in postpartum women who have delivered a singleton, live born infant within the last 12 weeks to 1 year and had a pregnancy complicated by gestational diabetes. The main question this study aims to answer is:

Is a Lifestyle Intervention or Metformin more effective for weight loss in postpartum women with recent gestational diabetes?

Researchers will compare a 6-month Lifestyle Intervention and Metformin to see if either intervention is more effective in achieving weight loss and improving health outcomes.

Participants will:

* Attend an in-person baseline visit to receive a Bluetooth-enabled scale and Fitbit, have blood drawn for testing, and have their height, weight, and blood pressure measured. Participants will also be asked to bring in their infant, and the study team will measure the infant's weight and length.
* Track diet, physical activity, and weight using the Fitbit and Looseit! apps.
* Attend weekly online group sessions for the first 4 weeks, then biweekly sessions.
* If not meeting weight loss goals, be randomized to either Enhanced Lifestyle Intervention or Metformin arms of the study.
* If randomized to Metformin, participants will attend one in-person meeting with the study provider, get blood drawn for testing, and undergo a urine pregnancy test before starting the medication.
* Continue with biweekly group sessions or have regular check-in calls.
* If randomized to the Enhanced Lifestyle Intervention, participants will get a free Instacart membership, a 1:1 session with the study health counselor focused on meal planning and free grocery delivery once a week for the remainder of the study.
* Participants will meet every other week via Zoom with the health counselor and other participants in the enhanced lifestyle arm.
* At the end of the 6 months, all participants will come for an in-person visit to get blood drawn for testing. Participants will also be asked to bring in their infant, and the study team will measure the infant's weight and length.

Detailed description: Once enrollment is complete (consent signed), participants will complete the baseline online medical history form and 9 questionnaires available on-line.

Baseline: Participants will come for an in-person visit to the GW School of Public Health and receive a Bluetooth-enabled digital scale and a Fitbit activity tracker. Research staff will help participants set up a study Fitbit and Looseit! account. Participants will undergo serum blood collection (10 ml) for HgbA1c and lipids. Participants will also be asked to bring in their infant, and the study team will measure the infant's weight and length. Participants will be asked to use this Fitbit and Looseit! account for the duration of the study to track their diet, activity, and weight. Study staff will access this data, review participant progress, and provide feedback as needed.

Start: All participants will begin with the DPP-based Lifestyle Intervention (LI). The program includes weekly online 45-minute Zoom group sessions for 4 weeks. After week 4, Zoom group sessions will be biweekly. The goal is a 2% weight loss at 4 weeks and a 3% weight loss at 6 weeks. These sessions will be led by a trained health counselor who is part of the research team. The health counselor will review the Fitbit Tracker information and provide tips for improving dietary intake and physical activity via email or text messaging based on the participant's preference.

At the end of week 4 and week 6, participants will submit their weight through Bluetooth-enabled scales.

If they have reached their weight loss goal, they will continue with the lifestyle intervention (LI) with online Zoom group sessions held every other week for the remainder of the intervention (for a total of a 6-month intervention).

After 4 or 6 weeks, participants who have not yet reached their weight loss goal (non-responders) will be randomly assigned to one of two intervention groups:

1. DPP-based Enhanced Lifestyle intervention (eLI)

   OR
2. Metformin (850 mg daily x 7 days, then 850 mg twice daily) orally

Enhanced Lifestyle Intervention (eLI): Participants will continue with the same components as the Lifestyle Intervention (LI), with the addition of guidance on healthy meal planning and online grocery shopping, including one free delivery per week. If randomized to this group, participants will continue to have group sessions every other week with others in the eLI arm of the study for the duration of the study (5 or 4.5 months, depending on when they were randomized to the Metformin arm) for a total of a 6-month intervention. Group sessions will last 45-60 minutes each. These sessions will be led by a trained health counselor in the research team. The health counselor will review the Fitbit Tracker and looseit! information and provide tips for improving dietary intake and physical activity via email or text messaging based on the participant's preference.

Metformin Arm: Participants in this arm will have an individual in-person session with the health counselor and study provider where they will receive information about 1) the risks and benefits of Metformin, 2) instructions on how to obtain Metformin from the Investigational Drug Pharmacy at the George Washington School of Medicine and Health Sciences. After the in-person session, participants will visit the LabCorp facility on the GW Foggy Bottom campus to provide 5 mL of serum for creatinine and liver function testing, as well as undergo a urine pregnancy test. Participants with abnormal liver function tests (ALT outside 4-36 U/L or AST outside 8-33 U/L), eGFR \< 60 ml/min, or a positive pregnancy test will be ineligible for Metformin. Once lab results are reviewed, participants will be placed on Metformin by mouth (850 mg daily x 7 days, then 850 mg twice daily). Tablets will be distributed by the Investigational Drug Pharmacy at the George Washington School of Medicine and Health Sciences. This is the current dosage prescribed for weight loss in the clinical setting.

Participants on Metformin will have a 15-minute follow-up call one week after starting the medication to answer additional questions, assess for any medication side effects, and assess for adherence, and then 15-minute follow-up calls by the research team every 2 weeks. Participants will be educated that it is safe to continue to breastfeed while on Metformin, as recommended by the American College of Obstetricians and Gynecologists published recommendations on postpartum care following a pregnancy with GDM. There are no group sessions for this group. Participants will be encouraged to continue practicing healthy lifestyle behaviors learned during the first 4 weeks of the intervention.

End of study: At the end of the study (6 months), participants will complete one questionnaire with updates about their health since their baseline questionnaire and will also complete 9 online questionnaires (same as baseline). Participants will come for an in-person visit where they will be asked to bring their pill container, if they were randomized to the Metformin arm, and provide a 10 ml serum sample for HbA1c, and lipids via LabCorp. Participants will also be asked to bring in their infant, and the study team will measure the infant's weight and length.

Eligibility criteria: Inclusion Criteria:

* Mothers between 8 weeks and 12 months postpartum from a pregnancy complicated by GDM will be recruited. The research team will begin recruiting women who are at least 8 weeks postpartum to provide time to describe the study and answer any questions. Mothers who want to participate will be enrolled in the study between 12 weeks and 12 months postpartum.
* BMI of 25 kg/m2 to 45 kg/m2
* Singleton delivery
* Participants must also have a working cell phone, be willing to accept email or text messages attend Zoom calls, and be willing to be potentially randomized to drug therapy with Metformin.

Exclusion Criteria:

* Pregnant or planned pregnancy within the next 6 months.
* Participation in any other weight loss program or taking weight loss medication.
* Normal or underweight BMI (BMI \< 24.9 kg/m2)
* Multi-fetal (twins or triplets) gestation
* Women with type 1 or type 2 diabetes, malignancy, other serious co-morbidities (advanced kidney disease, NYHA class 3-4 CHF, advanced COPD), schizophrenia or other major psychiatric disease, and substance abuse or AIDS.
* Women whose infants have significant medical conditions, such as congenital heart disease, renal impairment, or hepatic impairment.

Primary outcomes:
measure: Mean weight change at 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Change in physical activity
timeFrame: 6 months
measure: Change in blood pressure
timeFrame: 6 months
measure: Change in A1c
timeFrame: 6 months
measure: Change in lipids
timeFrame: 6 months
measure: Change in quality of life
timeFrame: 6 months
measure: Change in depression score
timeFrame: 6 months
measure: Change in diet quality
timeFrame: 6 months
measure: Breastfeeding
timeFrame: 6 months
measure: Adherence to Metformin treatment
timeFrame: 4.5 to 5 months
measure: Infant weight
timeFrame: 6 months
measure: Infant length
timeFrame: 6 months
Other outcomes:
Locations:
city: Washington
country: United States
facility: Milken Institute School of Public Health - The George Washington University
state: District of Columbia
Study officials:
affiliation: The George Washington University
name: Wanda Nicholson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ferrara A. Increasing prevalence of gestational diabetes mellitus: a public health perspective. Diabetes Care. 2007 Jul;30 Suppl 2:S141-6. doi: 10.2337/dc07-s206. No abstract available.
citation: DeSisto CL, Kim SY, Sharma AJ. Prevalence estimates of gestational diabetes mellitus in the United States, Pregnancy Risk Assessment Monitoring System (PRAMS), 2007-2010. Prev Chronic Dis. 2014 Jun 19;11:E104. doi: 10.5888/pcd11.130415.
citation: HAPO Study Cooperative Research Group; Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, Hadden DR, McCance DR, Hod M, McIntyre HD, Oats JJ, Persson B, Rogers MS, Sacks DA. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008 May 8;358(19):1991-2002. doi: 10.1056/NEJMoa0707943.
citation: Heida KY, Franx A, van Rijn BB, Eijkemans MJ, Boer JM, Verschuren MW, Oudijk MA, Bots ML, van der Schouw YT. Earlier Age of Onset of Chronic Hypertension and Type 2 Diabetes Mellitus After a Hypertensive Disorder of Pregnancy or Gestational Diabetes Mellitus. Hypertension. 2015 Dec;66(6):1116-22. doi: 10.1161/HYPERTENSIONAHA.115.06005. Epub 2015 Oct 12.
citation: Hedderson M, Ehrlich S, Sridhar S, Darbinian J, Moore S, Ferrara A. Racial/ethnic disparities in the prevalence of gestational diabetes mellitus by BMI. Diabetes Care. 2012 Jul;35(7):1492-8. doi: 10.2337/dc11-2267. Epub 2012 May 22.
citation: Bellamy L, Casas JP, Hingorani AD, Williams D. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet. 2009 May 23;373(9677):1773-9. doi: 10.1016/S0140-6736(09)60731-5.
citation: Hamman RF, Wing RR, Edelstein SL, Lachin JM, Bray GA, Delahanty L, Hoskin M, Kriska AM, Mayer-Davis EJ, Pi-Sunyer X, Regensteiner J, Venditti B, Wylie-Rosett J. Effect of weight loss with lifestyle intervention on risk of diabetes. Diabetes Care. 2006 Sep;29(9):2102-7. doi: 10.2337/dc06-0560.
citation: Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403. doi: 10.1056/NEJMoa012512.
citation: Elmer PJ, Grimm R Jr, Laing B, Grandits G, Svendsen K, Van Heel N, Betz E, Raines J, Link M, Stamler J, et al. Lifestyle intervention: results of the Treatment of Mild Hypertension Study (TOMHS). Prev Med. 1995 Jul;24(4):378-88. doi: 10.1006/pmed.1995.1062.
citation: Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M; Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001 May 3;344(18):1343-50. doi: 10.1056/NEJM200105033441801.
citation: Whelton PK, Appel LJ, Espeland MA, Applegate WB, Ettinger WH Jr, Kostis JB, Kumanyika S, Lacy CR, Johnson KC, Folmar S, Cutler JA. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). TONE Collaborative Research Group. JAMA. 1998 Mar 18;279(11):839-46. doi: 10.1001/jama.279.11.839.
citation: Cassina M, Dona M, Di Gianantonio E, Litta P, Clementi M. First-trimester exposure to metformin and risk of birth defects: a systematic review and meta-analysis. Hum Reprod Update. 2014 Sep-Oct;20(5):656-69. doi: 10.1093/humupd/dmu022. Epub 2014 May 25.
citation: Ali MK, Echouffo-Tcheugui J, Williamson DF. How effective were lifestyle interventions in real-world settings that were modeled on the Diabetes Prevention Program? Health Aff (Millwood). 2012 Jan;31(1):67-75. doi: 10.1377/hlthaff.2011.1009.
citation: Phelan S, Hagobian T, Brannen A, Hatley KE, Schaffner A, Munoz-Christian K, Tate DF. Effect of an Internet-Based Program on Weight Loss for Low-Income Postpartum Women: A Randomized Clinical Trial. JAMA. 2017 Jun 20;317(23):2381-2391. doi: 10.1001/jama.2017.7119.
citation: Castorino K, Jovanovic L. Pregnancy and diabetes management: advances and controversies. Clin Chem. 2011 Feb;57(2):221-30. doi: 10.1373/clinchem.2010.155382. Epub 2010 Dec 9.
citation: Syngelaki A, Nicolaides KH, Balani J, Hyer S, Akolekar R, Kotecha R, Pastides A, Shehata H. Metformin versus Placebo in Obese Pregnant Women without Diabetes Mellitus. N Engl J Med. 2016 Feb 4;374(5):434-43. doi: 10.1056/NEJMoa1509819.
citation: American College of Obstetricians and Gynecologists Committee on Practice Bulletins--Obstetrics. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. Number 30, September 2001 (replaces Technical Bulletin Number 200, December 1994). Gestational diabetes. Obstet Gynecol. 2001 Sep;98(3):525-38.
citation: ACOG Committee Opinion No. 736: Optimizing Postpartum Care. Obstet Gynecol. 2018 May;131(5):e140-e150. doi: 10.1097/AOG.0000000000002633.
citation: ACOG Committee Opinion No. 435: postpartum screening for abnormal glucose tolerance in women who had gestational diabetes mellitus. Obstet Gynecol. 2009 Jun;113(6):1419-1421. doi: 10.1097/AOG.0b013e3181ac06b6.
citation: Nicholson WK, Beckham AJ, Hatley K, Diamond M, Johnson LS, Green SL, Tate D. The Gestational Diabetes Management System (GooDMomS): development, feasibility and lessons learned from a patient-informed, web-based pregnancy and postpartum lifestyle intervention. BMC Pregnancy Childbirth. 2016 Sep 21;16(1):277. doi: 10.1186/s12884-016-1064-z.
citation: Refuerzo JS, Viteri OA, Hutchinson M, Pedroza C, Blackwell SC, Tyson JE, Ramin SM. The effects of metformin on weight loss in women with gestational diabetes: a pilot randomized, placebo-controlled trial. Am J Obstet Gynecol. 2015 Mar;212(3):389.e1-9. doi: 10.1016/j.ajog.2014.12.019. Epub 2014 Dec 16.
citation: Hale TW, Kristensen JH, Hackett LP, Kohan R, Ilett KF. Transfer of metformin into human milk. Diabetologia. 2002 Nov;45(11):1509-14. doi: 10.1007/s00125-002-0939-x. Epub 2002 Sep 25.
citation: Gardiner SJ, Kirkpatrick CM, Begg EJ, Zhang M, Moore MP, Saville DJ. Transfer of metformin into human milk. Clin Pharmacol Ther. 2003 Jan;73(1):71-7. doi: 10.1067/mcp.2003.9.
citation: Briggs GG, Ambrose PJ, Nageotte MP, Padilla G, Wan S. Excretion of metformin into breast milk and the effect on nursing infants. Obstet Gynecol. 2005 Jun;105(6):1437-41. doi: 10.1097/01.AOG.0000163249.65810.5b.