NNC0487-0111 for Type 2 Diabetes

Recruiting at 95 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Novo Nordisk A/S

Must be taking: Metformin, SGLT2 inhibitors

Must not be taking: Diabetes, obesity medications

Disqualifiers: Uncontrolled diabetic retinopathy, hypoglycaemic unawareness, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 36 weeks

432 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it requires that you have been on a stable dose of metformin, with or without an SGLT2 inhibitor, for at least 90 days before joining. Other diabetes or obesity medications are not allowed within 90 days before the trial.

What data supports the effectiveness of the drug NNC0487-0111 for Type 2 Diabetes?

Incretin-based therapies, which include drugs similar to NNC0487-0111, have shown to improve blood sugar control and help with weight management in people with Type 2 Diabetes. These therapies work by enhancing the body's natural response to food intake, and they have additional benefits like reducing inflammation and supporting heart and liver health. ^{1 2 3 4 5}

What makes the drug NNC0487-0111 unique for treating Type 2 Diabetes?

NNC0487-0111, also known as Amycretin, is unique because it is a long-acting glucagon-like peptide-1 (GLP-1) derivative designed for once-daily administration, which helps lower blood sugar levels and potentially increases beta-cell mass in the pancreas, offering a longer duration of action compared to other GLP-1 treatments. ^{5 6 7 8 9}

What is the purpose of this trial?

The study will look at how well different doses of a new medicine called NNC0487-0111 help lower the blood sugar and body weight in people with type 2 diabetes. NNC0487-0111 is a new medicine which cannot be prescribed by doctors but has previously been tested in humans. Participants will either get NNC0487-0111, which is given as tablets or as injections, or placebo. Which treatment the participant get is decided by chance.The study will last for about 43 weeks.

Research Team

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

This trial is for individuals with type 2 diabetes who are interested in testing a new medication, NNC0487-0111. Participants will be involved in the study for approximately 43 weeks and must meet specific health criteria to join.

Inclusion Criteria

Body mass index between greater or equal to 23.0 and below 50.0 kg/m^2

I was diagnosed with type 2 diabetes more than 6 months ago.

Able and willing to adhere to the protocol including wearing a continuous glucose monitoring (CGM) device provided for the study

Exclusion Criteria

I have severe diabetic eye problems that are not under control.

I haven't taken diabetes or obesity drugs not listed in the criteria in the last 90 days.

Known hypoglycaemic unawareness as indicated by the investigator according to Clarke's questionnaire question

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either NNC0487-0111 or placebo, administered as tablets or injections, to evaluate the effect on blood sugar and body weight

36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• NNC0487-0111

Trial Overview The study tests how well different doses of NNC0487-0111 lower blood sugar and body weight when administered orally or by injection compared to a placebo. Treatment assignments are randomized.

Participant Groups

Group I: NNC0487-0111 subcutaneous dose 6 Experimental Treatment 1 Intervention

NNC0487-0111 subcutaneous dose 6 treatment

Group II: NNC0487-0111 subcutaneous dose 5 Experimental Treatment 1 Intervention

NNC0487-0111 subcutaneous dose 5 treatment

Group III: NNC0487-0111 subcutaneous dose 4 Experimental Treatment 1 Intervention

NNC0487-0111 subcutaneous dose 4 treatment

Group IV: NNC0487-0111 subcutaneous dose 3 Experimental Treatment 1 Intervention

NNC0487-0111 subcutaneous dose 3 treatment

Group V: NNC0487-0111 subcutaneous dose 2 Experimental Treatment 1 Intervention

NNC0487-0111 subcutaneous dose 2 treatment

Group VI: NNC0487-0111 subcutaneous dose 1 Experimental Treatment 1 Intervention

NNC0487-0111 subcutaneous dose 1 treatment

Group VII: NNC0487-0111 oral dose 3 Experimental Treatment 1 Intervention

NNC0487-0111 oral dose 3 treatment

Group VIII: NNC0487-0111 oral dose 2 Experimental Treatment 1 Intervention

NNC0487-0111 oral dose 2 treatment

Group IX: NNC0487-0111 oral dose 1 Experimental Treatment 1 Intervention

NNC0487-0111 oral dose 1 treatment

Group X: Placebo oral Placebo Group 1 Intervention

Placebo for oral treatment

Group XI: Placebo subcutaneous Placebo Group 1 Intervention

Placebo for subcutaneous treatment

Who Is Running the Clinical Trial?

Novo Nordisk A/S

Lead Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Findings from Research

Incretin-based therapies, including oral DPP-4 inhibitors and injectable GLP-1 receptor agonists, are effective in managing Type 2 diabetes by improving glycemic control and aiding in weight management, particularly addressing the reduced incretin effect seen in diabetic patients.

These therapies not only help regulate blood sugar levels but also show potential benefits for inflammation, cardiovascular health, liver function, sleep, and brain health, indicating a broader impact beyond just diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incretin-based therapies. Stonehouse, AH., Darsow, T., Maggs, DG.[2022]

Incretin therapies are emerging treatments for type 2 diabetes (T2D) that could provide new options for patients, especially as the disease is increasingly diagnosed at younger ages in the UK.

The article emphasizes the importance of understanding the clinical evidence and recommendations for incretin therapies, which can help diabetes nurses offer more effective treatment strategies for managing T2D.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incretin-based therapies for type 2 diabetes: a nurse's perspective. Hodgkiss, J.[2011]

Incretin-based therapies, particularly GLP-1 analogues and DPP-4 inhibitors, have significantly improved the management of type 2 diabetes by effectively lowering hemoglobin A1c levels, promoting weight loss, and having a low risk of hypoglycemia.

Recent meta-analyses have alleviated concerns regarding an elevated risk of pancreatitis associated with these therapies, confirming their safety and tolerability compared to other diabetes medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incretin manipulation in diabetes management. Pappachan, JM., Raveendran, AV., Sriraman, R.[2020]

The U.S. FDA has approved six classes of oral medications for type 2 diabetes, with metformin and lifestyle changes recommended as the first-line treatments according to a consensus by the American Diabetes Association and the European Association for the Study of Diabetes.

New therapies in development, including incretin therapies and agents targeting metabolic syndrome, show promise for improving treatment options for type 2 diabetes, especially for patients struggling with weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of type 2 diabetes: new and future developments in treatment. Liao, EP.[2022]

In a study involving 210 subjects with Type 2 diabetes, liraglutide, a once-daily GLP-1 analogue, showed improvements in glycaemic control and weight loss comparable to metformin, particularly at higher doses.

Liraglutide was found to be safe and well tolerated, with no major hypoglycaemic episodes reported, although some patients experienced mild nausea or vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of liraglutide (NN2211), a long-acting GLP-1 analogue, on glycaemic control and bodyweight in subjects with Type 2 diabetes. Feinglos, MN., Saad, MF., Pi-Sunyer, FX., et al.[2022]

NN2211, a long-acting GLP-1 derivative, effectively reduced blood glucose levels in ob/ob and db/db mice, showing sustained antihyperglycemic effects for 24 hours after administration.

In db/db mice, NN2211 not only decreased blood glucose but also significantly increased beta-cell mass and proliferation, suggesting a potential mechanism for improved insulin production, while body weight remained unchanged.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The long-acting GLP-1 derivative NN2211 ameliorates glycemia and increases beta-cell mass in diabetic mice. Rolin, B., Larsen, MO., Gotfredsen, CF., et al.[2018]

In a study involving 10 subjects with type 2 diabetes, the long-acting GLP-1 derivative NN2211 significantly increased insulin secretion and improved beta-cell responsiveness to glucose compared to placebo.

NN2211's effects on insulin secretion rates were comparable to those observed in nondiabetic individuals, suggesting it effectively mimics normal physiological responses to elevated blood sugar levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The GLP-1 derivative NN2211 restores beta-cell sensitivity to glucose in type 2 diabetic patients after a single dose. Chang, AM., Jakobsen, G., Sturis, J., et al.[2019]

In a study of 63 newly diagnosed type 2 diabetes patients treated for 12 weeks, liraglutide showed better control of blood glucose fluctuations compared to NPH, with significant reductions in measures like MAGE and SDBG.

While liraglutide and NPH both improved overall glycemic control similarly, liraglutide had a lower incidence of hypoglycemia and was associated with gastrointestinal side effects and some weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of liraglutide vs. NPH in combination with metformin on blood glucose fluctuations assessed using continuous glucose monitoring in patients with newly diagnosed type 2 diabetes. Ma, Z., Chen, R., Liu, Y., et al.[2022]

In a study involving 11 patients with type 2 diabetes, the long-acting GLP-1 derivative NN2211 significantly reduced fasting plasma glucose levels and meal-related glucose levels, demonstrating its efficacy as a glucose-lowering agent.

NN2211 works by increasing insulin secretion, delaying gastric emptying, and suppressing glucagon secretion, with a half-life of about 10 hours, indicating its potential for effective management of blood sugar levels in diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bedtime administration of NN2211, a long-acting GLP-1 derivative, substantially reduces fasting and postprandial glycemia in type 2 diabetes. Juhl, CB., Hollingdal, M., Sturis, J., et al.[2022]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Incretin-based therapies. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Incretin-based therapies for type 2 diabetes: a nurse's perspective. [2011]

3. United States pubmed.ncbi.nlm.nih.gov

Incretin manipulation in diabetes management. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Management of type 2 diabetes: new and future developments in treatment. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Effects of liraglutide (NN2211), a long-acting GLP-1 analogue, on glycaemic control and bodyweight in subjects with Type 2 diabetes. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

The long-acting GLP-1 derivative NN2211 ameliorates glycemia and increases beta-cell mass in diabetic mice. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

The GLP-1 derivative NN2211 restores beta-cell sensitivity to glucose in type 2 diabetic patients after a single dose. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Effect of liraglutide vs. NPH in combination with metformin on blood glucose fluctuations assessed using continuous glucose monitoring in patients with newly diagnosed type 2 diabetes. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Bedtime administration of NN2211, a long-acting GLP-1 derivative, substantially reduces fasting and postprandial glycemia in type 2 diabetes. [2022]