The Separate and Combined Effects of Long-term GIP and GLP-1 Receptor Activation in Patients with Type 2 Diabetes

NCT05078255 | Completed DMC

• 1 other identifier: U1111-1259-1491
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

Due to reports of a severely reduced insulinotropic effect of the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) in type 2 diabetes (T2D), GIP has not been considered therapeutically viable in T2D. Recently, however, tirzepatide, a novel dual incretin receptor agonist (activating both the GIP receptor and the glucagon-like peptide 1 (GLP-1) receptor) demonstrated massive improvements in glycaemic control and robust body weight losses; greater than observed with the GLP-1 receptor agonist semaglutide. However, the contribution of GIP receptor activation to these effects remains unknown. The present study will evaluate the glucose-lowering effect of GIP in the context of pharmacological GLP-1 receptor activation in patients with T2D.

Conditions

Type 2 Diabetes; Obesity

Outcome Measures

Primary Outcomes (1)

• Mean glucose levels (assessed by blinded continuous glucose monitoring (CGM))

  The primary outcome is change in 14-day mean glucose levels (assessed by CGM) during the last 14 days of the intervention period as compared to 14-day mean glucose levels during the last 14 days of the run-in period.

  14-day mean glucose levels during the last 14 days of the intervention period as compared to 14-day mean glucose levels during the last 14 days of the run-in period.

Study Arms (4)

placebo injections + placebo infusion

PLACEBO COMPARATOR

Other: Semaglutide 1.34 mg/ml placebo; Other: GIP placebo

Semaglutide 1.34 mg/ml injections + GIP infusion

EXPERIMENTAL

Drug: Semaglutide 1.34 MG/ML [Ozempic]; Drug: Glucose-dependent insulinotropic polypeptide (GIP)

placebo injections + GIP infusion

EXPERIMENTAL

Drug: Glucose-dependent insulinotropic polypeptide (GIP); Other: Semaglutide 1.34 mg/ml placebo

Semaglutide 1.34 mg/ml injections + placebo infusion

EXPERIMENTAL

Drug: Semaglutide 1.34 MG/ML [Ozempic]; Other: GIP placebo

Interventions

Semaglutide 1.34 MG/ML [Ozempic] DRUG

Semaglutide 1.34 mg/ml

Also known as: Glucose-dependent insulinotropic polypeptide (GIP)

Semaglutide 1.34 mg/ml injections + GIP infusion; Semaglutide 1.34 mg/ml injections + placebo infusion

Glucose-dependent insulinotropic polypeptide (GIP) DRUG

GIP

Semaglutide 1.34 mg/ml injections + GIP infusion; placebo injections + GIP infusion

Semaglutide 1.34 mg/ml placebo OTHER

Saline

placebo injections + GIP infusion; placebo injections + placebo infusion

GIP placebo OTHER

Saline

Semaglutide 1.34 mg/ml injections + placebo infusion; placebo injections + placebo infusion

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
• Men and women 18 to 74 years of age (both inclusive) at the time of signing informed consent
• Diagnosed with type 2 diabetes for at least six months
• Treated with diet and exercise and/or stable metformin and/or sodium-glucose cotransporter 2 (SGLT-2) inhibitor and/or dipeptidyl-peptidase 4 inhibitor (DPP-4i) and/or sulfonylureas (SU) treatment for at least 3 months If treated with DPP-4i and/or SU, this treatment must be paused for 14 days prior to first CGM period in the trial
• HbA1c ≥48 to ≤91 mmol/mol
• BMI ≥25 to ≤50 kg/m2
• Stable body weight (less than 3 kg self-reported change during the previous 90 days)

You may not qualify if:

• Diagnosed with type 1 diabetes
• Known or suspected hypersensitivity to trial product or related products
• Acute decompensation of glycaemic control requiring immediate intensification of treatment to prevent acute complications of diabetes (e.g. diabetes ketoacidosis) which required help from doctor or hospitalisation within 90 days prior to screening
• Previous participation in this trial. Participation is defined as signed informed consent. Participation is allowed if the protocol is updated to a newer version
• Participation in another clinical trial within 90 days before screening
• Woman who are pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive methods (intrauterine devices or hormonal contraception (oral contraceptive pills, implants, transdermal patches, vaginal rings or long-acting injections))
• If previously treated with GLP-1RA, information about the time and reason for stopping will be collected. Based upon this, the eligibility will be judged by the investigator
• Participation in an organised weight reduction programme within 3 months before screening
• Any disorder which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol
• Anticipated change in lifestyle (e.g. smoking, eating or exercise pattern) during the trial
• Any laboratory safety parameter at screening outside the below extended laboratory ranges, see laboratory manual for specific values
• Albumin outside lower normal limit (LNL) -5% and upper normal limit (UNL) +5%
• Alanine aminotransferase (ALT) outside LNL -100% and UNL +50%
• Creatinine outside UNL +10%
• Haemoglobin outside LNL -5% and UNL +10%

Sponsors & Collaborators

• Asger Lund, MD: lead

Study Sites (1)

Center for Clinical Metabolic Research, Gentofte Hospital

Hellerup, Capital Region, DK-2900, Denmark

Location

Related Publications (1)

• Helsted MM, Gasbjerg LS, Vilsboll T, Nielsen CK, Forman JL, Christensen MB, Knop FK. Separate and combined effects of long-term GIP and GLP-1 receptor activation in patients with type 2 diabetes: a structured summary of a study protocol for a double-blind, randomised, placebo-controlled clinical trial. BMJ Open. 2023 Feb 27;13(2):e065736. doi: 10.1136/bmjopen-2022-065736.

  PMID: 36849212 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity

Interventions

semaglutide; Incretins

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate professor, MD PhD

Study Record Dates

• First Submitted: October 1, 2021
• First Posted: October 14, 2021
• Study Start: January 27, 2022
• Primary Completion: January 6, 2025
• Study Completion: January 24, 2025
• Last Updated: March 14, 2025

Record last verified: 2025-01

Locations

DK (1)