Hypertension in pregnancy, gestational diabetes Pregnancy and Childbirth
Conditions
Interventions
Current interventions as of 24/07/2026:
Part B: Intervention: (i) SGLT2i, oral dapagliflozin 10 mg once a day for 26 weeks
(ii) GLP-1, tirzepatide, weekly subcutaneous injections for 26 weeks. Starting dose will be 2.5mg for at least 4 weeks, with subsequent increases of 2.5 mg every 4 weeks based on symptom tolerance and
(ii) 52 weeks study duration with maximum duration on GLP-1 of 26 weeks
_____
Previous interventions:
1:1 randomisation of postpartum individuals, who had pregnancies complicated by hypertensive di
Sponsors
King's College London
King's College Hospital NHS Foundation Trust
Eligibility
Sex/Gender
Female
Age
18 Years to 120 Years
Inclusion criteria
Inclusion criteria: Current key inclusion criteria as of 24/07/2026: Part A: 1. Person with current pregnancy, or within six weeks of pregnancy, complicated by hypertension 2. Able to provide written informed consent 3. Age = 18 years 4. Body mass index >23kg/m² Part B: Postpartum person (including people not identifying as female) with: 1. Previous pregnancy complicated by hypertension in pregnancy and/or gestational diabetes (defined by National Institute for Health and Care Excellence) =12-months 2. Able to provide written informed consent 3. Age = 18 years 4. Completed breastfeeding 5. Body mass index =27kg/m² Study buddy: Study buddy (co-recruitment as selected by the postpartum person): 1. Age 18 years – 60 years 2. Body mass index =27kg/m² 3. Able to provide written informed consent 4. Person with =1 of the following pre-cardiovascular disease risk factor (NICE 2024): 4.1. Pre-hypertension (systolic blood pressure 120- 139 and/or diastolic blood pressure 80-89 mmHg) 4.2. Parent or sibling with diabetes or body mass index >30kg/m2 AND age > 25 years if African Caribbean, Black African, or South Asian or age > 40 years if any other ethnicity AND Haemoglobin A1c of 42-47 mmol/mol (6-6.4%) 4.3. Postpartum person with previous pregnancy complicated by hypertension in pregnancy and/or gestational diabetes >12-months _____ Previous key inclusion criteria: Part A: 1. Person with current pregnancy, or within 6 weeks of pregnancy, complicated by hypertension 2. Able to provide written informed consent 3. Age = 18 years 4. Body mass index >17 kg/m² Part B: Postpartum person (including people not identifying as female): 1. Previous pregnancy complicated by HDP and/or GDM (defined by NICE) =12 months 2. Able to provide written informed consent 3. Age =18 years 4. Completed breastfeeding 5. Body mass index >17 kg/m2 Study buddy: 1. Able to provide written informed consent 2. Age 18 – 60 years with =1 pre-CVD risk factor: 2.1. Pre-hypertension (systolic BP 120-139 mmHg and/or diastolic BP 80-89 mmHg) 2.2. Parent or sibling with diabetes or body mass index >30 kg/m2 AND age>40 years if White or age>25 years if African Caribbean, Black African, or South Asian AND Haemoglobin A1c =42-47 mmol/mol (6-6.4%) OR 2.3. Postpartum person with a previous pregnancy complicated by HDP and/or GDM >12 months 3. Body mass index >17 kg/m2
Exclusion criteria
Exclusion criteria: Current key exclusion criteria as of 24/07/2026: Part A: Pregnant or postpartum person (including people not identifying as female) with: 1. Diabetes (Type-1 or 2) 2. Chronic Kidney Disease or Heart failure and recommended routine SGLT2i 3. Severe hepatic impairment 4. Allergy to dapagliflozin (SGLT2i), tirzepatide (GLP-1) or its excipients 5. Hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption 6. Contraindication to postpartum enalapril, amlodipine, nifedipine, or labetalol - including allergy 7. Moving away from study site within 12 months 8. Planning pregnancy =6-months Part B: Postpartum person and study-buddies with: 1. Diabetes (Type-1 or 2), or history of diabetic ketoacidosis or hyperosmolar state or diabetic coma 2. Chronic Kidney Disease or Heart failure and recommended routine SGLT2i 3. Liver disease (AST or ALT > 2x upper limit of normal) 4. History of acute or chronic pancreatitis 5. Severe gastrointestinal disease 6. Oral medications with a narrow therapeutic window (e.g. warfarin, digoxin) 7. Any drug associated with hypoglycaemia (e.g. antimalarial agents, lithium) 8. Allergy to dapagliflozin (SGLT2i), tirzepatide (GLP-1), or its excipients 9. Pregnant*, planning pregnancy within 6 months or breastfeeding (females of childbearing potential* with a positive pregnancy test at screening) 10. Moving away from study site within 12 months 11. Severe hepatic impairment 12. Hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption 13. Use of GLP-1 receptor agonists within the past 3 months 14. History of organ transplantation * A pregnancy test (urine) will be performed for all persons of childbearing potential at all onsite visits and monthly at home tests performed. Study drugs will not be dispensed without a negative pregnancy test. Women randomised to tirzepatide on oral contraception will be counselled on the potential for reduced efficacy and advised to use a barrier method or switch to non-oral contraception methods _____ Previous key exclusion criteria: Part A: Pregnant or postpartum person (including people not identifying as female) with: 1. Diabetes (Type 1 or 2) 2. Chronic kidney disease or heart failure and recommended routine SGLT2i 3. Liver disease (AST/ALT >2x upper limit of normal) 4. Allergy to dapagliflozin or its excipients 5. Hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption 6. Moving away from the study site within 12 months 7. Severe hepatic impairment 8. Contraindication to postpartum enalapril, amlodipine, nifedipine, or labetalol - including allergy 9. Planning pregnancy =6 months Part B: Postpartum person (including people not identifying as female) and study-buddies with: 1. Diabetes (Type 1 or 2) 2. Chronic kidney disease or heart failure and recommended routine SGLT2i 3. Liver disease (AST/ALT > 2x upper limit of normal) 4. Allergy to dapagliflozin or its excipients 5. Hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption 6. Pregnant, planning pregnancy within 6 months or breastfeeding (females of childbearing potential* with a positive pregnancy test at screening) 7. Moving away from the study site within 12 months 8. Severe hepatic impairment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The overall recruitment rate of postpartum participants with hypertension in pregnancy and/or gestational diabetes (number of participants per site per month, assessed at end of study). Determined from screening logs with eligibility criteria met and reasons for exclusion reported at the end of the study, defined as a database lock. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current key secondary outcome(s) as of 24/07/2026: Process Endpoints: 1. Overall uptake and recruitment rate of study-buddies assessed at the end of the study. Determined from screening logs with eligibility criteria met and reasons for exclusion reported. 2. Longitudinal assessment of retention of postpartum participants and study-buddies across both arms (assessed at end of study) 3. Number of blood pressures, weights, pregnancy test results, urine-dip results (up to and including 26 weeks for each participant, total number assessed up to and including 52 weeks) from home results sent in by participants on the clinical portal (MyChart, or local patient electronic portal). 4. Number of returned blood and urine tests up to and including 26 weeks. 5. Evaluation of acceptability and experience of all study activities (For Part A: End of study survey and focus group at 16 weeks and for Part B: End of study survey with postpartum participants and study buddies at 52 weeks; focus group with postpartum participants, study buddies and health champions at 26 and 52 weeks*) 6. Study resource use: Contacts with health champions, time for health champion training, expenditure on printing (£), time (hours) on recruitment and data extraction, home testing kit use (up to and including 26 weeks and 52 weeks) Clinical Endpoints: 7. Adherence to (i) daily SGLT2i (intervention arm 1) and weekly injections of GLP-1 (intervention arm 2) assessed either at 26 weeks by a member of the research team pill-counting, by reviewing 4 weekly photographs of drug blister packs, or patient’s diaries. Adherence will also be assessed at 16 weeks in Part A and at 26 weeks in Part B using the Medication Adherence Report Scale-5 (MARS-5). 8. Pregnancy rate during the study period (Part B) and pregnancy outcomes (pregnancy tests performed 4 weekly, overall pregnancy rates assessed at end of study) recorded in Macro database 9. Longitudinal changes in BP and weight at 4 weekly intervals, and 26 and 52 | — |
Countries
England, United Kingdom
Outcome results
None listed