Obesity Treatment to Improve Diabetes

NCT05390307 | Completed

• 1 other identifier: RA-HM2021009
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

As the obesity pandemic continues unabated, one can expect to see an increase in the prevalence of TID/T2D and associated CKD. As a result, death will rise, preceded by an increase in kidney failure, requiring dialysis and renal transplantation. Innovative medical treatment may help prevent chronic kidney disease (CKD) across our healthcare system. The guideline of the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) suggest that patients with obesity, TID/ T2D, and CKD needed either glucagon-like peptide 1 receptor analogs (GLP1-RA) or sodium-glucose cotransport-2 inhibitors (SGLT2i). If neither achieve metabolic control, then the recommendation is to combine both drugs. The evidence base for combining GLP1RA and SGLT2i are not well developed, and hence the impact of the guidelines are limited. This study will provide evidence of discrete metabolic pathways by the GLP1RA/or SGLT2i alone or in combination contributed to metabolic control. The aim of this randomised control trial (RCT) is to test the impact of the combination of GLP1RA/SGLT2i on body weight and kidney damage, in patients with T1DM and CKD. In addition, we will explore associated changes in metabolic pathways with each of the treatments used in the RCT.

Conditions

Type 1 Diabetes

Keywords

Type 1 Diabetes Mellitus; Obesity; Chronic Kidney Disease

Outcome Measures

Primary Outcomes (1)

• Weight

  Percentage change in total body weight

  26 weeks

Secondary Outcomes (6)

• Glycaemia

  26 weeks

• Hypertension

  26 weeks

• Lipidaemia

  26 weeks

• Albuminuria

  26 weeks

• Waist circumference

  26 weeks

Study Arms (5)

GLP1RA alone

EXPERIMENTAL

Participants in the GLP1RA will be prescribed either Liraglutide 3.0mg or Semaglutide 1.0mg, whichever is licensed and available locally. The dose and titration will follow the usual clinical practice. The treatment will continue for 6 months.

Drug: Liraglutide / Semaglutide

SGLT2i alone

EXPERIMENTAL

Participants in the SGLT2i group will be prescribed dapagliflozin 5-10mg once daily for 6 months.

Drug: Dapagliflozin

GLP1RA/SGLT2i combination

EXPERIMENTAL

Participants in the combination GLP1RA and SGLT2i group will be prescribed liraglutide 3mg once daily or semaglutide1mg once weekly subcutaneous injection plus dapagliflozin 5-10mg for 6 months.

Drug: Liraglutide or Semaglutide / Dapagliflozin

GLP1RA/SGLT2i combination with intensive lifestyle changes

EXPERIMENTAL

Participants in the combination GLP1RA and SGLT2i and intensive weight loss groupwill be prescribed liraglutide 3mg once daily or semaglutide 1mg once weekly subcutaneous injection plus dapagliflozin 5-10mg together with an intensive dietary and lifestyle approach for 6 months. This typically involves dietary advice to reduce energy intake (and may includea period of partial or total meal replacement), accompanied -if available -by a physical activity programme, both supported by behavioural change techniqueswith regular professional contacts.

Drug: Liraglutide or Semaglutide / Dapagliflozin plus intensive weight loss nutrition

Usual Care

EXPERIMENTAL

Participants in the usual care arm will follow the best medical care by following the international guidelines for 6 months. This usually involves diet and exercise advice.

Other: Usual care

Interventions

Liraglutide / Semaglutide DRUG

Liraglutide 3mg once daily or semaglutide 1mg once weekly subcutaneous injection for 6 months.

Also known as: GLP1RA alone

GLP1RA alone

Dapagliflozin DRUG

Dapagliflozin 5-10 mg once daily for 6 months.

Also known as: SGLT2i alone

SGLT2i alone

Liraglutide or Semaglutide / Dapagliflozin DRUG

Combined treatment with Liraglutide 3mg once daily or semaglutide 1mg once weekly subcutaneous injection plus Dapagliflozin 5-10 mg once daily for 6 months.

Also known as: Combination of GLP1RA and SGLT2i

GLP1RA/SGLT2i combination

Liraglutide or Semaglutide / Dapagliflozin plus intensive weight loss nutrition DRUG

Liraglutide 3mg once daily or semaglutide 1mg once weekly subcutaneous injection plus Dapagliflozin 5-10 mg once daily for 6 months combined with intensive lifestyle changes.

Also known as: Combination of GLP1RA, SGLT2i and intensive weight loss nutrition

GLP1RA/SGLT2i combination with intensive lifestyle changes

Usual care OTHER

Usual standard care

Usual Care

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be considered eligible to participate in this study, a patient must:
• Be aged between 21-65 years,
• Have a BMI ≥ 25 kg/m2,
• Have established diagnosis of Type 1 Diabetes for at least 1 year before screening visit
• Insulin treatment for T1D - may be either via any FDA approved insulin pump (CSII) for at least 6 months prior to screening visit or via multiple daily insulin injections. All participants must be stable on insulin doses/ regimen for at least 3 months
• Have established diagnosis of Chronic Kidney Disease stage 1-4
• Able to give informed consent

You may not qualify if:

• Participants will be excluded if:
• Have been treated with GLP-1 or SGLT2i within the last 3 months and/or have a history of GLP1RA or SGLT2i intolerance
• Diagnosis of T2D or any other type of diabetes (other than type 1)
• Treatment with anti-obesity drugs within 12 weeks prior to randomisation
• Significant changes in the lifestyle (Diet or exercise pattern in within 3 months of the screening visit)
• Any self reported changes (gain or loss) in body weight \>5% within 3 months of screening visit
• eGFR ≤15 mL/min/1.73m2
• Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using or willing to use adequate contraceptive methods during the study period
• Experienced diabetic ketoacidosis within 6 months of screening visit
• Experienced sever hypoglycaemia within 6 months of screening visit
• Any of the following laboratory values at screening (liver chemistry \> 3X upper limit of normal, high Tg (. 5.7 mmol/L)
• Have terminal illness or are not primarily responsible for their own care
• Any other significant disease or disorder which in the opinion of the investigator, may either put the participants at risk or may influence the result of the study or the participant's ability to participate
• Untreated or uncontrolled hypothyroidism/hyperthyroidism defined as thyroid-stimulating hormone \>6 mIU/litre or \<0.4 mIU/litre
• Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (FMTC)

Sponsors & Collaborators

• Dasman Diabetes Institute: lead

Study Sites (1)

Dasman Diabetes Institute

Kuwait City, Al Asimah, 15462, Kuwait

Location

Related Publications (1)

• Al-Ozairi E, Narula K, Miras AD, Taghadom E, Samad AE, Al Kandari J, Alyosef A, Mashankar A, Al-Najim W, le Roux CW. Obesity Treatments to Improve Type 1 Diabetes (OTID): a randomized controlled trial of the combination of glucagon-like peptide 1 analogues and sodium-glucose cotransporter 2 inhibitors-protocol for Obesity Treatments to Improve Type 1 Diabetes (the OTID trial). Trials. 2024 Feb 16;25(1):129. doi: 10.1186/s13063-024-07930-3.

  PMID: 38365744 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Obesity; Renal Insufficiency, Chronic

Interventions

Liraglutide; semaglutide; dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Ebaa Al Ozairi

  Dasman Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: In this 6-month randomized control trial, 60 participants aged between 21-65 years, with a body mass index (BMI) above 25kg/m2 and T1D with CKD will be randomised to receive one of five possible treatments 1) Standard care (control), 2) GLP1RA alone, 3) SGLT2i alone, 4) combination of GLP1RA and SGLT2i, 5) combination of GLP1RA and SGLT2i with intensive lifestyle advice.

Study Record Dates

• First Submitted: May 14, 2022
• First Posted: May 25, 2022
• Study Start: April 1, 2023
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2024
• Last Updated: February 28, 2024

Record last verified: 2024-02

Locations

KU (1)