Rebalancing the Fat Content of the Heart and Muscles

NCT07065383 | Recruiting

• 1 other identifier: 3-034-24
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Traditional diabetes therapies focus on improving blood sugar control. However, many studies show that this may not be enough. New treatments focusing on weight loss have heralded better results. One of these treatments is Semaglutide and the investigators wish to examine its effects further in this study. The investigators propose to investigate what happens to the fat inside the heart and the leg muscles.

Conditions

Diabetes Mellitus Type 2

Outcome Measures

Primary Outcomes (1)

• 1H-magnetic resonance spectroscopy

  Non-invasive proton magnetic resonance spectroscopy (1H MRS) for assessment to determine the total intramyocellular fat

  From enrollment to the end of treatment at the end of 12 weeks

Secondary Outcomes (1)

• Intramyocellular lipid pool compartments

  From enrollment to the end of treatment at the end of 12 weeks

Study Arms (2)

Semaglutide administration plus dietary counselling and physical activity encouragement

PLACEBO COMPARATOR

Semaglutide administration plus dietary counselling and physical activity encouragement

Drug: Semaglutide administration plus dietary counselling and physical activity encouragement

Semaglutide and supervised training program

ACTIVE COMPARATOR

Semaglutide administration plus a personalised and supervised program of resistance and endurance training

Drug: Semaglutide plus a personalised and supervised program of resistance and endurance training

Interventions

Semaglutide administration plus dietary counselling and physical activity encouragement DRUG

Semaglutide administration plus dietary counselling and physical activity encouragement

Also known as: Semaglutide with dietary counselling and physical activity encouragement

Semaglutide administration plus dietary counselling and physical activity encouragement

Semaglutide plus a personalised and supervised program of resistance and endurance training DRUG

Semaglutide administration plus a personalised and supervised program of resistance and endurance training.

Also known as: Semaglutide plus personalised and supervised resistance and endurance training program

Semaglutide and supervised training program

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a confirmed diagnosis of type 2 diabetes established in the previous 10 years between the ages of 20 and 75
• HbA1c ≥ 53 mmol/mol (7%) typically on diet and/or metformin/sulphonylureas (and/or sodium-glucose cotransporter-2 inhibitors, Dipeptidyl peptidase 4 inhibitors, thiazolidinediones, but not on insulin)
• Patients who do not meet the WHO recommendations on physical activity (≤150 minutes per week) of moderate-vigorous physical activity (MVPA)
• Patients who have a BMI of ≥27 but with a body weight of less than 140kgs due to limitations of the scanner table weight limit
• Current or recent (within 3 months) eGFR \>30 mL/min/1.73m2)
• Able to understand written and spoken English

You may not qualify if:

• Any previously unknown cardiac condition other than mild valvular disease
• Any history of known coronary artery disease (including myocardial infarction and myocardial infarction with normal coronary arteries)
• Any relevant or untreated endocrine condition (i.e. Cushings)
• Impaired renal function (defined as estimated glomerular filtration rate of less than 30 mL/min/1.73m2)
• Blood pressure of more than 180/100 mmHg
• Patients on any other medication known to influence glucose or fatty acids metabolism (niacin, omega-3 fatty acids, other glucagon-like peptide-1 receptor agonists)
• Patients with any dietary habits that may interfere with the investigation (for example high fat vegan diets, as we know form prior research that they have very different intramyocellular fat storage compared to those on no dietary preferences)
• Patients with any history of any medical or surgical condition that in the judgement of the investigators may interfere with the exercise regime (i.e. peripheral vascular disease, arthritis), fatty acids metabolism (i.e. lipid storage diseases) or may compromise the safety of the participant (i.e. neurological syndromes for whom an intense exercise program could result in musculo-skeletal injury or accidents due to loss of balance).
• Patients with a sensitivity to Semaglutide (known hypersensitivity, diabetic retinopathy, pregnancy, history of pancreatitis or history of any cancer)
• Significant asthma or pulmonary disease
• Participants unable to cycle on the ergometer
• Unable to perform exercise testing (e.g. prosthetic limbs)
• Pregnancy, breastfeeding or considering pregnancy.
• Patients who have recently had gastrointestinal contrast or radionuclides
• Inability to lie flat or remain motionless for scanning procedures

Sponsors & Collaborators

• University of Aberdeen: lead
• NHS Grampian: collaborator

Study Sites (1)

Cardiac Research Office, Aberdeen Royal Infirmary

Aberdeen, Aberdeenshire, AB25 2ZD, United Kingdom

RECRUITING

Related Publications (25)

• Rodriguez-Gutierrez R, Montori VM. Glycemic Control for Patients With Type 2 Diabetes Mellitus: Our Evolving Faith in the Face of Evidence. Circ Cardiovasc Qual Outcomes. 2016 Sep;9(5):504-12. doi: 10.1161/CIRCOUTCOMES.116.002901. Epub 2016 Aug 23.

  PMID: 27553599 BACKGROUND

• von Gerichten J, West AL, Irvine NA, Miles EA, Calder PC, Lillycrop KA, Fielding BA, Burdge GC. The Partitioning of Newly Assimilated Linoleic and alpha-Linolenic Acids Between Synthesis of Longer-Chain Polyunsaturated Fatty Acids and Hydroxyoctadecaenoic Acids Is a Putative Branch Point in T-Cell Essential Fatty Acid Metabolism. Front Immunol. 2021 Oct 5;12:740749. doi: 10.3389/fimmu.2021.740749. eCollection 2021.

  PMID: 34675928 BACKGROUND

• Burdge GC, Wright P, Jones AE, Wootton SA. A method for separation of phosphatidylcholine, triacylglycerol, non-esterified fatty acids and cholesterol esters from plasma by solid-phase extraction. Br J Nutr. 2000 Nov;84(5):781-7.

  PMID: 11177194 BACKGROUND

• FOLCH J, LEES M, SLOANE STANLEY GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497-509. No abstract available.

  PMID: 13428781 BACKGROUND

• Johnson NA, Walton DW, Sachinwalla T, Thompson CH, Smith K, Ruell PA, Stannard SR, George J. Noninvasive assessment of hepatic lipid composition: Advancing understanding and management of fatty liver disorders. Hepatology. 2008 May;47(5):1513-23. doi: 10.1002/hep.22220.

  PMID: 18393289 BACKGROUND

• Boesch C, Slotboom J, Hoppeler H, Kreis R. In vivo determination of intra-myocellular lipids in human muscle by means of localized 1H-MR-spectroscopy. Magn Reson Med. 1997 Apr;37(4):484-93. doi: 10.1002/mrm.1910370403.

  PMID: 9094069 BACKGROUND

• Scally C, Abbas H, Ahearn T, Srinivasan J, Mezincescu A, Rudd A, Spath N, Yucel-Finn A, Yuecel R, Oldroyd K, Dospinescu C, Horgan G, Broadhurst P, Henning A, Newby DE, Semple S, Wilson HM, Dawson DK. Myocardial and Systemic Inflammation in Acute Stress-Induced (Takotsubo) Cardiomyopathy. Circulation. 2019 Mar 26;139(13):1581-1592. doi: 10.1161/CIRCULATIONAHA.118.037975.

  PMID: 30586731 BACKGROUND

• Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004 Jun;27(6):1487-95. doi: 10.2337/diacare.27.6.1487.

  PMID: 15161807 BACKGROUND

• Fillmer A, Hock A, Cameron D, Henning A. Non-Water-Suppressed 1H MR Spectroscopy with Orientational Prior Knowledge Shows Potential for Separating Intra- and Extramyocellular Lipid Signals in Human Myocardium. Sci Rep. 2017 Dec 4;7(1):16898. doi: 10.1038/s41598-017-16318-0.

  PMID: 29203776 BACKGROUND

• Blundell J, Finlayson G, Axelsen M, Flint A, Gibbons C, Kvist T, Hjerpsted JB. Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes Obes Metab. 2017 Sep;19(9):1242-1251. doi: 10.1111/dom.12932. Epub 2017 May 5.

  PMID: 28266779 BACKGROUND

• Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989-1002. doi: 10.1056/NEJMoa2032183. Epub 2021 Feb 10.

  PMID: 33567185 BACKGROUND

• Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, Hardt-Lindberg S, Hovingh GK, Kahn SE, Kushner RF, Lingvay I, Oral TK, Michelsen MM, Plutzky J, Tornoe CW, Ryan DH; SELECT Trial Investigators. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023 Dec 14;389(24):2221-2232. doi: 10.1056/NEJMoa2307563. Epub 2023 Nov 11.

  PMID: 37952131 BACKGROUND

• Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsboll T; SUSTAIN-6 Investigators. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016 Nov 10;375(19):1834-1844. doi: 10.1056/NEJMoa1607141. Epub 2016 Sep 15.

  PMID: 27633186 BACKGROUND

• Iacobellis G. Epicardial adipose tissue in contemporary cardiology. Nat Rev Cardiol. 2022 Sep;19(9):593-606. doi: 10.1038/s41569-022-00679-9. Epub 2022 Mar 16.

  PMID: 35296869 BACKGROUND

• Dube JJ, Amati F, Stefanovic-Racic M, Toledo FG, Sauers SE, Goodpaster BH. Exercise-induced alterations in intramyocellular lipids and insulin resistance: the athlete's paradox revisited. Am J Physiol Endocrinol Metab. 2008 May;294(5):E882-8. doi: 10.1152/ajpendo.00769.2007. Epub 2008 Mar 4.

  PMID: 18319352 BACKGROUND

• Goodpaster BH, He J, Watkins S, Kelley DE. Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J Clin Endocrinol Metab. 2001 Dec;86(12):5755-61. doi: 10.1210/jcem.86.12.8075.

  PMID: 11739435 BACKGROUND

• Bergman BC, Perreault L, Hunerdosse DM, Koehler MC, Samek AM, Eckel RH. Increased intramuscular lipid synthesis and low saturation relate to insulin sensitivity in endurance-trained athletes. J Appl Physiol (1985). 2010 May;108(5):1134-41. doi: 10.1152/japplphysiol.00684.2009. Epub 2010 Mar 18.

  PMID: 20299618 BACKGROUND

• Petersen KF, Dufour S, Morino K, Yoo PS, Cline GW, Shulman GI. Reversal of muscle insulin resistance by weight reduction in young, lean, insulin-resistant offspring of parents with type 2 diabetes. Proc Natl Acad Sci U S A. 2012 May 22;109(21):8236-40. doi: 10.1073/pnas.1205675109. Epub 2012 Apr 30.

  PMID: 22547801 BACKGROUND

• Amati F, Dube JJ, Alvarez-Carnero E, Edreira MM, Chomentowski P, Coen PM, Switzer GE, Bickel PE, Stefanovic-Racic M, Toledo FG, Goodpaster BH. Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: another paradox in endurance-trained athletes? Diabetes. 2011 Oct;60(10):2588-97. doi: 10.2337/db10-1221. Epub 2011 Aug 26.

  PMID: 21873552 BACKGROUND

• Levelt E, Mahmod M, Piechnik SK, Ariga R, Francis JM, Rodgers CT, Clarke WT, Sabharwal N, Schneider JE, Karamitsos TD, Clarke K, Rider OJ, Neubauer S. Relationship Between Left Ventricular Structural and Metabolic Remodeling in Type 2 Diabetes. Diabetes. 2016 Jan;65(1):44-52. doi: 10.2337/db15-0627. Epub 2015 Oct 5.

  PMID: 26438611 BACKGROUND

• Ozasa N, Furukawa Y, Morimoto T, Tadamura E, Kita T, Kimura T. Relation among left ventricular mass, insulin resistance, and hemodynamic parameters in type 2 diabetes. Hypertens Res. 2008 Mar;31(3):425-32. doi: 10.1291/hypres.31.425.

  PMID: 18497461 BACKGROUND

• Summers SA, Nelson DH. A role for sphingolipids in producing the common features of type 2 diabetes, metabolic syndrome X, and Cushing's syndrome. Diabetes. 2005 Mar;54(3):591-602. doi: 10.2337/diabetes.54.3.591.

  PMID: 15734832 BACKGROUND

• Dube JJ, Amati F, Toledo FG, Stefanovic-Racic M, Rossi A, Coen P, Goodpaster BH. Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide. Diabetologia. 2011 May;54(5):1147-56. doi: 10.1007/s00125-011-2065-0. Epub 2011 Feb 17.

  PMID: 21327867 BACKGROUND

• King DS, Dalsky GP, Clutter WE, Young DA, Staten MA, Cryer PE, Holloszy JO. Effects of exercise and lack of exercise on insulin sensitivity and responsiveness. J Appl Physiol (1985). 1988 May;64(5):1942-6. doi: 10.1152/jappl.1988.64.5.1942.

  PMID: 3292505 BACKGROUND

• Cheng YJ, Imperatore G, Geiss LS, Saydah SH, Albright AL, Ali MK, Gregg EW. Trends and Disparities in Cardiovascular Mortality Among U.S. Adults With and Without Self-Reported Diabetes, 1988-2015. Diabetes Care. 2018 Nov;41(11):2306-2315. doi: 10.2337/dc18-0831. Epub 2018 Aug 21.

  PMID: 30131397 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

semaglutide; Endurance Training

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Dana Dawson, DM

  University of Aberdeen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexander Davidson, DM

CONTACT

+441224559573; alexander.davidson@abdn.ac.uk

Amelia E Rudd, MSc, PhD

CONTACT

01224559573; cardiologyresearch@abdn.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2025
• First Posted: July 15, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: April 30, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)