A Trial Within Cohort Feasibility Study Design Comparing Standard of Care Versus Weight Loss (Achieved Through Tirzepatide) for Obesity-related Hypertension in Young Adults (SOLUTION-Pilot)

Standard of Care or Weight Loss Drug Therapy in Obesity-related Hypertension - Pilot Study

Hypertension is the leading risk factor for death globally, affecting approximately 30% of adults in the United Kingdom. Obesity is also a serious and ongoing epidemic, with global obesity rates having more than tripled in men and doubled in women, since 1975. In the United Kingdom, 64% of the adult population are overweight or obese. Hypertension and obesity share a well-established association, with obesity being responsible for the development of hypertension in 40-78% of cases. In young adults, this link between body size and blood pressure (BP) is much stronger that in older adults. Since overweight and obesity are among the most common and modifiable causes of high BP, weight loss induced by lifestyle-changes is recommended for overweight or obese patients with hypertension. However, lifestyle interventions, even when successful, result in only moderate weight loss, which is not maintained in the majority of cases. A meta-analysis of randomised controlled trials demonstrated that lifestyle-interventions lead to an average net weight reduction of 5.1 kg, accompanied by a significant, but modest, ~4 mmHg reduction in BP. Weight loss interventions could play a crucial role in the treatment of obesity-related hypertension in young adults.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists, originally developed for the treatment of type 2 diabetes, are safe and clinically effective anti-obesity drugs. Recent data show a 10-20% placebo-adjusted reduction in body weight in overweight or obese adults without diabetes using the GLP-1 analogue semaglutide or the dual GLP-1/GIP receptor agonist tirzepatide, with the majority of weight loss achieved within the initial six months. The substantial weight loss induced by these drugs is accompanied by a significant reduction in BP. Two recent meta-analyses showed that semaglutide is associated with a ~5 mmHg placebo-adjusted reduction in clinic systolic BP (SBP). A sub-study of the SURMOUNT-1 trial reported a ~10 mmHg reduction in 24-h ambulatory SBP with tirzepatide. Most participants in these studies were normotensive or had well-controlled hypertension. Furthermore, antihypertensive medication use declined amongst those receiving anti-obesity drugs meaning the BP-lowering effect of weight loss, elicited by these drugs, is probably underestimated. These data suggest that the new anti-obesity drugs could be effective in managing overweight or obesity-related hypertension. Furthermore, it may be possible to cure hypertension in at least some young adults, removing the need for life-long antihypertensive treatment. However, the magnitude and time course of BP reduction elicited by these new anti-obesity drugs remain uncertain.

The primary aim of this feasibility study is to assess the extent and trajectory of BP reduction achieved through intensive weight loss in overweight or obese adults with stage 1 hypertension and compare this to current standard of care measures which uses anti-hypertensive medications and lifestyle advice. The study will utilise a modified trial within cohort approach, using patients based within the clinical pharmacology/hypertension service at Addenbrooke's Hospital, Cambridge.

Study Overview

• Status: Recruiting
• Conditions: Hypertension; Obesity & Overweight
• Intervention / Treatment: Drug: Tirzepatide; Drug: Anti-Hypertensive medications

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Recruiting
      • Cambridge University Hospitals NHS Foundation Trust
      • Contact: James Goodman, MRCP PhD; Phone Number: +44 01223 336806; Email: james.goodman11@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Eligibility criteria for randomisation

Inclusion Criteria:

• Aged 18 to 40 years (inclusive)
• Body mass index (BMI) ≥27 kg/m2
• Clinical diagnosis of primary (essential) hypertension as per NICE guidance
• Unattended brachial SBP ≥135 and/or DBP ≥85 mmHg and <160/100 mmHg
• Maximum of one antihypertensive medication

Exclusion Criteria:

• Anything in medical notes suggesting unsuitable in the opinion of the investigator

Eligibility criteria for participation in weight loss arm

Inclusion criteria:

• Written informed consent
• Aged 18 to 40 years (inclusive)
• Body mass index ≥27 kg/m2
• Clinical diagnosis of primary (essential) hypertension as per NICE guidance
• Unattended brachial SBP ≥135 and/or DBP ≥85 mmHg and <160/100 mmHg
• Maximum of one antihypertensive medication

Exclusion criteria:

The presence of any of the following will preclude participant inclusion:

• Known or suspected secondary hypertension
• Hypersensitivity to any of the study drugs or excipients
• Currently taking drugs likely to have interactions with tirzepatide
• Diagnosis of type 1 or type 2 diabetes mellitus or current usage of insulin or other injectable drugs for the treatment of diabetes such as but not limited to GLP-1 and GIP receptor agonists
• Prior or planned surgical, endoscopic and/or device-based therapy treatment for obesity
• Self-reported, intentional or unintentional, change in body weight (over ~10%) within ~three months of screening
• Known heart failure or clinically significant valvular heart disease
• Implanted pacemaker or implantable cardioverter defibrillator (ICD)
• Second or third-degree AV block, sino-atrial block, sick sinus syndrome
• Known active malignancy including thyroid cancer
• Known renal impairment (creatinine >150µmol/L)
• Clinically significant neurological disease
• History of scleroderma
• Participants on anticoagulant therapy
• Known history of pancreatitis
• Known inflammatory bowel disease
• History of gallstones (unless previous cholecystectomy)
• Severe gastroparesis or gastric emptying abnormality
• Family history of multiple endocrine neoplasia
• Needle-phobia
• Planned pregnancy, current pregnancy, or breastfeeding
• Current involvement in the active treatment phase of other research studies
• Any other clinical reason which may preclude entry in the opinion of the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tirzepatide [weight loss arm]; 6 months of treatment with a combined GLP-1/GIP receptor agonist, tirzepatide	Drug: Tirzepatide; 2.5mg for 4 weeks, 5mg for 4 weeks, 7.5mg for 4 weeks, 10mg for 12 weeks
Active Comparator: Lifestyle advice and anti-hypertensive medications [standard of Care arm]	Drug: Anti-Hypertensive medications; Anti-hypertensive drug therapy as per local and national guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ambulatory systolic blood pressure	Change in daytime ambulatory systolic blood pressure in the weight loss arm	Baseline to week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ambulatory diastolic blood pressure	Change in daytime ambulatory diastolic blood pressure in the weight loss arm	Baseline to week 24
Clinic systolic blood pressure	Changes in clinic systolic blood pressure in the weight loss arm	Baseline to week 24
Clinic diastolic blood pressure	Changes in clinic diastolic blood pressure in the weight loss arm	Baseline to week 24
Clinic mean arterial pressure	Changes in clinic mean arterial pressure in the weight loss arm	Baseline to week 24
Unattended systolic blood pressure	Changes in unattended systolic blood pressure in the weight loss arm	Baseline to week 24
Unattended diastolic blood pressure	Changes in unattended diastolic blood pressure in the weight loss arm	Baseline to week 24
Unattended mean arterial pressure	Changes in unattended mean arterial pressure in the weight loss arm	Baseline to week 24
Body weight	Changes in body weight in the weight loss arm	Baseline to week 24
Body fat	Changes in body fat in the weight loss arm	Baseline to week 24
Waist:hip ratio	Changes in waist:hip ratio in the weight loss arm	Baseline to week 24
Cardiac output	Changes in cardiac output in the weight loss arm	Baseline to week 24
Peripheral vascular resistance	Changes in peripheral vascular resistance in the weight loss arm	Baseline to week 24
Pulse wave analysis / pulse wave velocity	Changes in markers of pulse wave analysis and pulse wave velocity in the weight loss arm	Baseline to week 24
Heart rate variability	Changes in heart rate variability in the weight loss arm	Baseline to week 24
Renin	Changes in plasma renin in the weight loss arm	Baseline to week 24
Aldosterone	Changes in plasma aldosterone in the weight loss arm	Baseline to week 24
Plasma metanephrines	Changes in plasma metanephrines in the weight loss arm	Baseline to week 24
Leptin	Changes in leptin in the weight loss arm	Baseline to week 24
Insulin	Changes in plasma insulin in the weight loss arm	Baseline to week 24
Lipid profile	Changes in the lipid profile in the weight loss arm	Baseline to week 24
HbA1C	Changes in HbA1C in the weight loss arm	Baseline to week 24
Estimated glomerular filtration rate	Changes in eGFR in the weight loss arm	Baseline to week 24
N-terminal pro-B-type natriuretic peptide	Changes in NT-proBNP in the weight loss arm	Baseline to week 24
Urine albumin:creatinine ratio	Change in urine albumin:creatinine ratio in the weight loss arm	Baseline to week 24
24-hour urine sodium	Change in 24-hour urine sodium in the weight loss arm	Baseline to week 24
24-hour urine aldosterone	Change in 24-hour urine aldosterone in the weight loss arm	Baseline to week 24
Antihypertensive medications	Change in number of antihypertensive medications	Baseline to week 24
Quality of life measures	Changes in quality of life questionnaire scores in the weight loss arm	Baseline to week 24
Ambulatory systolic blood pressure	Between-group comparison in ambulatory sytolic blood pressure	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
Ambulatory diastolic blood pressure	Between-group comparison in ambulatory diastolic blood pressure	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
Clinic systolic blood pressure	Between-group comparison in clinic systolic blood pressure	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
Clinic diastolic blood pressure	Between-group comparison in clinic diastolic blood pressure	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
Clinic mean arterial pressure	Between-group comparison in clinic mean arterial pressure	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
Unattended systolic blood pressure	Between-group comparison in unattended systolic blood pressure	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
Unattended diastolic blood pressure	Between-group comparison in unattended diastolic blood pressure	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
Unattended mean arterial pressure	Between-group comparison in mean arterial pressure	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
Body weight	Between-group body weight	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
Body fat	Between-group comparison in body fat	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
Waist:hip ratio	Between-group comparison in waist:hip ratio	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
Cardiac output	Between-group comparison in cardiac output	At week 24 (weight loss arm) and 6 months (standard of care arm)
Peripheral vascular resistance	Between-group comparison in peripheral vascular resistance	At week 24 (weight loss arm) and 6 months (standard of care arm)
Pulse wave analysis / pulse wave velocity	Between-group comparison in markers of pulse wave analysis and pulse wave velocity	At week 24 (weight loss arm) and 6 months (standard of care arm)
Heart rate variability	Between-group comparison in heart rate variability	At week 24 (weight loss arm) and 6 months (standard of care arm)
Plasma renin	Between-group comparison in plasma renin	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
Plasma aldosterone	Between-group comparison in plasma aldosterone	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
Plasma metanephrines	Between-group comparison in plasma metanephrines	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
Lipid profile	Between-group comparison in lipid profile	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
HbA1C	Between-group comparison in HbA1C	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
Estimated glomerular filtration rate	Between-group comparison in eGFR	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
N-terminal pro-B-type natriuretic peptide	Between-group comparison in NT-proBNP	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
Urine albumin:creatinine ratio	Between-group comparison in urine albumin:creatinine ratio	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
24-hour urine sodium	Between-group comparison in 24-hour urine sodium	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
24-hour urine aldosterone	Between-group comparison in 24-hour urine aldosterone	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
Number of antihypertensive medications	Between-group comparison in the number of anti-hypertensive medications	Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm)
Quality of life measures	Between-group comparison in quality of life questionnaire scores	At week 24 (weight loss arm) and 6 months (standard of care arm)

Collaborators and Investigators

• Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Collaborators: National Institute for Health Research, United Kingdom

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: January 6, 2026
• First Submitted That Met QC Criteria: January 18, 2026
• First Posted (Actual): January 23, 2026

Study Record Updates

• Last Update Posted (Actual): January 29, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: GLP-1; obesity; overweight; hypertension; tirzepatide
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Hypertension; Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide
• Other Study ID Numbers: R+D: A097457, REC: 25/WA/0268

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Following publication, the data that support the findings of this study will be available from the Chief Investigator/corresponding author upon reasonable request
• IPD Sharing Access Criteria: Following publication, the data that support the findings of this study will be available from the Chief Investigator/corresponding author upon reasonable request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No