Type 2 DiabetesNCT05078255
The Separate and Combined Effects of Long-term GIP and GLP-1 Receptor Activation in Patients with Type 2 Diabetes
A study testing Semaglutide 1.34 MG/ML [Ozempic] and Glucose-dependent insulinotropic polypeptide (GIP) in people with Type 2 Diabetes and Obesity, run by Asger Lund, MD at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 74 years
- Conditions the study is for
- Type 2 Diabetes, Obesity
- What is being tested?
- Semaglutide 1.34 MG/ML [Ozempic] and Glucose-dependent insulinotropic polypeptide (GIP)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 61 participants
- Where
- 1 siteDenmark
- Study dates
- 27 Jan 2022to 24 Jan 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- For an eligible participant, all exclusion criteria must be answered "no".
- 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
Show all 40Show fewer
- 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%
- Leukocytes outside LNL -20% and UNL +20%
- Thrombocytes outside LNL -15% and UNL +15%
- Bilirubin (total) outside UNL +15%
- Amylase ≥ UNL +100%
- Untreated or uncontrolled hypothyroidism/hyperthyroidism defined as thyroid-stimulating hormone (TSH) <0.4 mIU/L or > 6 mIU/L
- Obesity related to endocrinologic disorders (e.g. Cushing Syndrome)
- Any blood draw in excess of 25 mL in the past month, or donation of blood or plasma in excess of 400 mL within the 90 days preceding screening
- Use of any prescription or non-prescription medication (apart from oral contraceptives, routine vitamins, occasional use of paracetamol, acetylsalicylic acid, or ibuprofen) which could interfere with pharmacokinetic or pharmacodynamic results, as judged by the investigator, such as:
- herbal products and non-routine vitamins
- Glucose lowering medication (except metformin)
- medication that may cause weight gain, including systemic corticosteroids, tricyclic antidepressants, and atypical antipsychotics
- orlistat, zonisamide, topiramate, phentermine, lorcaserin, bupropion, naltrexone or other weight loss drugs
- Blood pressure and lipid lowering agents (e.g. statins) drugs are allowed if treatment has been stable for ≥ 1 month prior to screening and treatment should preferably be kept unchanged during the trial
- Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2
- History of pancreatitis (acute or chronic)
- History of major depressive disorder or other severe psychiatric disorders, e.g. schizophrenia or bipolar disorder within the last 2 years or lifetime history of suicide attempt
- Surgery scheduled for the trial duration period, except for minor, non-gastrointestinal surgical procedures at the discretion of the investigator
- Sitting blood pressure (after resting for at least 5 minutes) ≥160 mmHg systolic or ≥ 100 mmHg diastolic or heart rate of ≥ 90 beats/min after resting for at least 5 minutes (if white-coat hypertension is suspected, one repeat measurement is allowed; last measure being conclusive and to be recorded in the case report form (CRF))
- Cancer (past or present, except basal cell skin cancer or squamous cell skin cancer), which in the investigator's opinion could interfere with the results of the trial
- Known or suspected alcohol abuse within 1 year from screening (defined as regular intake of more than 14 units weekly for men and 7 units weekly for women - one unit of alcohol equals about 300 mL of beer or lager, one glass (100 ml) of wine, or 25 ml spirits) or a positive result of an alcohol test
- Known or suspected drug/chemical substance abuse within 1 year from screening
- Inability or unwillingness to perform self-injection at the screening visit (with a placebo test pen)
- Mental incapacity, language barriers or unwillingness to comply with the requirements of the protocol, which may preclude adequate understanding or co-operation during the trial, as judged by the investigator
- Investigator, any sub-investigators, research assistants, pharmacist, trial coordinators, other staff, sponsor staff or relatives thereof directly or indirectly involved in the conduct of the trial cannot participate in the trial
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Center for Clinical Metabolic Research, Gentofte Hospital
Hellerup, Capital Region, DK-2900
About this study
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
- Being tested
- Semaglutide 1.34 MG/ML [Ozempic], Glucose-dependent insulinotropic polypeptide (GIP), Semaglutide 1.34 mg/ml placebo, GIP placebo
- Medical subject headings
- Diabetes Mellitus, Type 2, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Semaglutide 1.34 MG/ML [Ozempic]Drug
Also called Glucose-dependent insulinotropic polypeptide (GIP)
Semaglutide 1.34 mg/ml
Glucose-dependent insulinotropic polypeptide (GIP)Drug
GIP
Semaglutide 1.34 mg/ml placeboOther
Saline
GIP placeboOther
Saline
| Study group | Role | What they receive |
|---|---|---|
| placebo injections + placebo infusion | Placebo comparator | Not described Receives: Other: Semaglutide 1.34 mg/ml placebo; Other: GIP placebo |
| Semaglutide 1.34 mg/ml injections + GIP infusion | Experimental | Not described Receives: Drug: Semaglutide 1.34 MG/ML [Ozempic]; Drug: Glucose-dependent insulinotropic polypeptide (GIP) |
| placebo injections + GIP infusion | Experimental | Not described Receives: Drug: Glucose-dependent insulinotropic polypeptide (GIP); Other: Semaglutide 1.34 mg/ml placebo |
| Semaglutide 1.34 mg/ml injections + placebo infusion | Experimental | Not described Receives: Drug: Semaglutide 1.34 MG/ML [Ozempic]; Other: GIP placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2021
- Study start27 Jan 2022
- Primary completion6 Jan 2025
- Study completion24 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asger Lund, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Asger Lund, MD, University Hospital, Gentofte, Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05078255
- Sponsor's protocol ID
- U1111-1259-1491
- Status last verified
- Jan 2025
- First submitted
- 1 Oct 2021
- Last updated
- 14 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Helsted MM, Fonnesbech-Wulff C, Schaltz NL, Lund IW, Forman JL, Nielsen CK, Englund A, Hartmann B, Vilsboll T, Holst JJ, Lund AB, Christensen MB, Knop FK, Gasbjerg LS. Effects of a 6-week subcutaneous infusion of native GIP alone or as add-on to semaglutide in people with type 2 diabetes: a single-centre, double-blind, parallel-group, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2026 Jul;14(7):581-593. doi: 10.1016/S2213-8587(26)00075-6. Epub 2026 May 22.
PubMed 42173109Helsted 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.
PubMed 36849212
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Separate and Combined Effects of Long-term GIP and GLP-1 Receptor Activation in Patients with Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT05078255
- Acronym / sponsor ID
- U1111-1259-1491
- Conditions
- Type 2 Diabetes, Obesity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Asger Lund, MDUniversity, hospital or other
- Study start
- 27 Jan 2022 (actual)
- Primary completion
- 6 Jan 2025 (actual)
- Study completion
- 24 Jan 2025 (actual)
- First posted
- 14 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
- BMI ≥25 to ≤50 kg/m2
- Stable body weight (less than 3 kg self-reported change during the previous 90 days)
Key exclusion criteria (40 listed)
- For an eligible participant, all exclusion criteria must be answered "no".
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Semaglutide 1.34 MG/ML [Ozempic]Also: Glucose-dependent insulinotropic polypeptide (GIP)Semaglutide 1.34 mg/ml | Drug | Semaglutide 1.34 mg/ml injections + GIP infusion, Semaglutide 1.34 mg/ml injections + placebo infusion |
| Glucose-dependent insulinotropic polypeptide (GIP)GIP | Drug | Semaglutide 1.34 mg/ml injections + GIP infusion, placebo injections + GIP infusion |
| Semaglutide 1.34 mg/ml placeboSaline | Other | placebo injections + GIP infusion, placebo injections + placebo infusion |
| GIP placeboSaline | Other | Semaglutide 1.34 mg/ml injections + placebo infusion, placebo injections + placebo infusion |
Primary outcome
Mean glucose levels (assessed by blinded continuous glucose monitoring (CGM))
Time frame: 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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2025.
- Derived from this study: PubMed 42173109Helsted MM, Fonnesbech-Wulff C, Schaltz NL, Lund IW, Forman JL, Nielsen CK, Englund A, Hartmann B, Vilsboll T, Holst JJ, Lund AB, Christensen MB, Knop FK, Gasbjerg LS. Effects of a 6-week subcutaneous infusion of native GIP alone or as add-on to semaglutide in people with type 2 diabetes: a single-centre, double-blind, parallel-group, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2026 Jul;14(7):581-593. doi: 10.1016/S2213-8587(26)00075-6. Epub 2026 May 22.
- Derived from this study: PubMed 36849212Helsted 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Semaglutide 1.34 MG/ML [Ozempic] and Glucose-dependent insulinotropic polypeptide (GIP) in people with Type 2 Diabetes and Obesity, run by Asger Lund, MD at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean glucose levels (assessed by blinded continuous glucose monitoring (CGM)) (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05078255, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2025.