Diabetes Medications for Type 2 Diabetes

Recruiting in Palo Alto (17 mi)

+1 other location

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: University of Alabama at Birmingham

Must not be taking: Insulin, SGLT2 inhibitors

Disqualifiers: Unstable diabetic retinopathy, macrovascular disease, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests three treatments (Insulin glargine, Metformin, Dorzagliatin) on people with type 2 diabetes to see if they can control nighttime blood sugar levels. These treatments work by either providing insulin, reducing sugar production, or improving natural blood sugar regulation.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are on insulin therapy, SGLT2 inhibitors, long-acting GLP-1 analogues, or certain other medications that affect glucose metabolism. It's best to discuss your current medications with the study team to see if they are allowed.

What data supports the effectiveness of the drug Dorzagliatin, HMS5552, Insulin Glargine, Lantus, Basaglar, Rezvoglar, Metformin, Glucophage, Fortamet, Glumetza, Riomet for treating type 2 diabetes?

Research shows that insulin glargine (Lantus) is effective and safe for people with type 2 diabetes, especially when combined with other diabetes medications. Studies found it helps control blood sugar levels in patients who were not well-managed on other treatments. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Research shows that insulin glargine (including Basaglar and Lantus) and dorzagliatin have been studied for safety in people with type 2 diabetes. These studies generally indicate that these medications are safe for human use, although some users may experience adverse events. ^{1 2 6 7 8}

What makes the drug dorzagliatin unique for treating type 2 diabetes?

Dorzagliatin is unique because it is a glucokinase activator that helps control blood sugar by activating enzymes in the pancreas and liver in a way that depends on glucose levels. This mechanism is different from other diabetes medications, which often target insulin directly or work through other pathways. ^{8 9 10 11 12}

Research Team

Eligibility Criteria

This trial is for adults with type 2 diabetes who have a BMI between 25-40, an HbA1C of ≤9%, and are on specific diabetes medications or lifestyle therapy. It's not for those taking drugs that affect blood sugar, have unstable diabetic eye disease, kidney issues, heart problems, GI disorders/surgery, severe chronic diseases, anemia or undiagnosed symptoms. Pregnant/breastfeeding individuals and those on insulin or certain other medications can't join.

Inclusion Criteria

My HbA1C is 9% or lower, and I'm on a diet, exercise plan, metformin, or SU.

Your body mass index (BMI) is between 25 and 40.

My HbA1C is 9% or lower and I'm on specific diabetes medications.

Exclusion Criteria

I am not currently taking any TZD medications.

You are pregnant, breastfeeding, or have other health conditions that prevent you from taking part in the study.

I am on insulin therapy.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomly assigned to one of three treatment groups (Insulin, Metformin, or Dorzagliatin) for 8 weeks to assess the effects on nighttime blood sugar levels.

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dorzagliatin (Anti-diabetic agent)
• Insulin Glargine (Insulin)
• Metformin (Anti-diabetic agent)

Trial Overview The study tests three treatments to manage night time blood sugars in type 2 diabetes over eight weeks: Insulin Glargine injected once daily; Metformin taken twice daily with meals; Dorzagliatin also taken twice daily. Participants will be randomly assigned to one group and doses adjusted to maintain safe fasting blood sugar levels.

Participant Groups

Group I: Dorzagliatin Experimental Treatment 1 Intervention

Group II: Insulin Glargine Active Control 1 Intervention

Group III: Metformin Active Control 1 Intervention

Dorzagliatin is already approved in China for the following indications:

Approved in China as Dorzagliatin for:

• Type 2 diabetes mellitus

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Kierstin Kennedy

University of Alabama at Birmingham

Chief Medical Officer since 2022

MD

S. Dawn Bulgarella

University of Alabama at Birmingham

Chief Executive Officer since 2023

BSc in Commerce and Business Administration from the University of Alabama, MS in Health Administration from the University of Alabama at Birmingham

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

James E. Ryan

University of Virginia

Chief Executive Officer since 2018

J.D. from Harvard Law School

Nikki Hastings

University of Virginia

Chief Medical Officer since 2018

Ph.D. in Biomedical Engineering from University of Virginia

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Dr. Griffin P. Rodgers

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Chief Executive Officer since 2007

MD, M.A.C.P.

Dr. Griffin P. Rodgers

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Chief Medical Officer since 2007

MD, M.A.C.P.

Findings from Research

In a study involving 1,291 patients with type 1 and type 2 diabetes, LY2963016 insulin glargine (LY IGlar) showed similar immunogenicity profiles to Lantus® insulin glargine (IGlar), with low levels of anti-insulin glargine antibodies observed in both groups.

There were no significant differences in clinical outcomes or safety between LY IGlar and IGlar, indicating that both treatments are equally effective and safe for managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of immunogenicity of LY2963016 insulin glargine compared with Lantus® insulin glargine in patients with type 1 or type 2 diabetes mellitus. Ilag, LL., Deeg, MA., Costigan, T., et al.[2018]

In a 24-week phase III study involving 756 patients with type 2 diabetes, LY2963016 insulin glargine (LY IGlar) demonstrated non-inferiority to the reference product Lantus(®) (IGlar) in reducing HbA1c levels, indicating it is equally effective for glucose control.

Both LY IGlar and IGlar had similar safety profiles, with no significant differences in adverse events, weight change, or hypoglycemia, suggesting that LY IGlar is a safe alternative to IGlar for patients with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Similar efficacy and safety of LY2963016 insulin glargine and insulin glargine (Lantus®) in patients with type 2 diabetes who were insulin-naïve or previously treated with insulin glargine: a randomized, double-blind controlled trial (the ELEMENT 2 study). Rosenstock, J., Hollander, P., Bhargava, A., et al.[2022]

In a pilot study involving 52 patients with Type 2 diabetes poorly controlled on premixed insulin, switching to insulin glargine combined with oral antidiabetic drugs (OADs) significantly improved glycaemic control, as evidenced by a notable decrease in HbA1c levels in both treatment groups (A and B).

The study found no significant differences in hypoglycaemia rates between the treatment groups, indicating that insulin glargine plus OADs is a safe alternative to premixed insulin therapy, with high patient satisfaction leading to a majority opting to continue their assigned treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and treatment satisfaction of once-daily insulin glargine plus one or two oral antidiabetic agents versus continuing premixed human insulin in patients with type 2 diabetes previously on long-term conventional insulin therapy: the Switch pilot study. Schiel, R., Müller, UA.[2022]

In a pilot study of 52 patients with Type 2 diabetes, switching from premixed insulin to insulin glargine combined with oral antidiabetic drugs (OADs) led to significant reductions in HbA1c levels, indicating improved glycaemic control.

The study found no significant differences in hypoglycaemia rates between the treatment groups, suggesting that insulin glargine plus OADs is a safe alternative to premixed insulin for patients with inadequate glycaemic control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and treatment satisfaction of once-daily insulin glargine plus one or two oral antidiabetic agents versus continuing premixed human insulin in patients with Type 2 diabetes previously on long-term conventional insulin therapy: the SWITCH Pilot Study. Schiel, R., Müller, UA.[2022]

In a phase III trial involving 536 insulin-naive Chinese patients with type 2 diabetes, LY2963016 insulin glargine (LY IGlar) demonstrated non-inferiority to Lantus (IGlar) in reducing HbA1c levels over 24 weeks, with both treatments achieving similar significant reductions.

Both LY IGlar and IGlar had comparable safety profiles, with no significant differences in adverse events, hypoglycemia, or weight gain, indicating that LY IGlar is a safe and effective alternative to IGlar for managing blood sugar levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of LY2963016 insulin glargine versus insulin glargine (Lantus) in Chinese adults with type 2 diabetes: A phase III, randomized, open-label, controlled trial. Feng, W., Chen, W., Jiang, S., et al.[2022]

In a 24-week study involving 756 patients with type 2 diabetes, Basaglar® (LY IGlar) and Lantus® (SA IGlar) showed similar efficacy and safety profiles for both older (≥65 years) and younger (<65 years) patients.

Patients aged ≥65 years required a lower basal insulin dose and experienced less weight gain compared to those <65 years, but there were no significant differences in treatment effects between the two age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Similar Efficacy and Safety of Basaglar&#174; and Lantus&#174; in Patients with Type 2 Diabetes in Age Groups (&lt;&#8201;65&#160;Years,&#8201;&#8805;&#8201;65&#160;Years): A Post Hoc Analysis from the ELEMENT-2 Study. Pollom, RK., Costigan, T., Lacaya, LB., et al.[2020]

The follow-on insulin glargine (Basaglar) has seen increased uptake among users, rising from 8.2% in 2017 to 24.8% in 2020, while the use of the originator insulin (Lantus) has decreased, indicating a shift in prescribing patterns.

Users of the follow-on insulin had poorer baseline health profiles and experienced higher rates of adverse events compared to users of the originator insulin, suggesting that further research is needed to understand the implications of these differences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilization, user characteristics, and adverse outcomes of insulin glargine originators and follow-on drug in patients with diabetes in the United States. Rai, A., Nam, YH., Mendelsohn, AB., et al.[2023]

Dorzagliatin significantly reduced glycated hemoglobin levels by 0.66% and fasting plasma glucose by 6.77 mg/dL in patients with type 2 diabetes mellitus, based on a meta-analysis of 3 studies involving 1333 patients.

The treatment was well tolerated, showing a good safety profile for liver and kidney function, although there was a slightly higher risk of adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dorzagliatin for Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Phase II/III Trials. Lin, F., He, R., Ling, B., et al.[2023]

In drug-naïve patients with type 2 diabetes, treatment with dorzagliatin resulted in a 65.2% probability of achieving drug-free diabetes remission after 52 weeks, indicating its effectiveness in maintaining stable glycaemic control.

Key factors contributing to this remission included significant improvements in insulin secretion and glucose homeostasis, as evidenced by increased time in range (TIR) from 60% to over 80%, highlighting dorzagliatin's positive impact on β-cell function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetes remission in drug-naïve patients with type 2 diabetes after dorzagliatin treatment: A prospective cohort study. Zeng, J., Gan, S., Mi, N., et al.[2023]

In a study of veterans with type 2 diabetes, combining GLP-1 receptor agonists and SGLT2 inhibitors led to a significant 1% reduction in HbA1c levels after 12 weeks, indicating improved glycemic control.

The combination therapy also resulted in a notable weight loss of about 5 kg (5%) and a significant decrease in systolic blood pressure over the study period, demonstrating additional health benefits beyond blood sugar management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of GLP-1 Receptor Agonists and SGLT2 Inhibitors Among Veterans With Type 2 Diabetes. McCulley, L., Hurren, KM.[2023]

Dorzagliatin is an oral glucokinase activator that improves blood sugar control in type 2 diabetes by activating glucokinase in the pancreas and liver, and it works in a glucose-dependent way.

In September 2022, dorzagliatin was approved in China for use as a standalone treatment and as an add-on to metformin for adults with type 2 diabetes, marking a significant milestone in its development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dorzagliatin: First Approval. Syed, YY.[2022]

In a phase 1 trial involving 15 patients with type 2 diabetes and obesity, the combination of dorzagliatin and sitagliptin was found to be safe and well-tolerated, with no increase in adverse events compared to sitagliptin alone.

The study demonstrated no clinically meaningful pharmacokinetic interactions between dorzagliatin and sitagliptin, suggesting that their co-administration could improve glycemic control in diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I open-label clinical trial to study drug-drug interactions of Dorzagliatin and Sitagliptin in patients with type 2 diabetes and obesity. Chen, L., Zhang, J., Sun, Y., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Evaluation of immunogenicity of LY2963016 insulin glargine compared with Lantus® insulin glargine in patients with type 1 or type 2 diabetes mellitus. [2018]

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

Similar efficacy and safety of LY2963016 insulin glargine and insulin glargine (Lantus®) in patients with type 2 diabetes who were insulin-naïve or previously treated with insulin glargine: a randomized, double-blind controlled trial (the ELEMENT 2 study). [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and treatment satisfaction of once-daily insulin glargine plus one or two oral antidiabetic agents versus continuing premixed human insulin in patients with type 2 diabetes previously on long-term conventional insulin therapy: the Switch pilot study. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and treatment satisfaction of once-daily insulin glargine plus one or two oral antidiabetic agents versus continuing premixed human insulin in patients with Type 2 diabetes previously on long-term conventional insulin therapy: the SWITCH Pilot Study. [2022]

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

Efficacy and safety of LY2963016 insulin glargine versus insulin glargine (Lantus) in Chinese adults with type 2 diabetes: A phase III, randomized, open-label, controlled trial. [2022]

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

Similar Efficacy and Safety of Basaglar&#174; and Lantus&#174; in Patients with Type 2 Diabetes in Age Groups (&lt;&#8201;65&#160;Years,&#8201;&#8805;&#8201;65&#160;Years): A Post Hoc Analysis from the ELEMENT-2 Study. [2020]

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

Utilization, user characteristics, and adverse outcomes of insulin glargine originators and follow-on drug in patients with diabetes in the United States. [2023]

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

Dorzagliatin for Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Phase II/III Trials. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Diabetes remission in drug-naïve patients with type 2 diabetes after dorzagliatin treatment: A prospective cohort study. [2023]

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

Safety and Efficacy of GLP-1 Receptor Agonists and SGLT2 Inhibitors Among Veterans With Type 2 Diabetes. [2023]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Dorzagliatin: First Approval. [2022]

12. England pubmed.ncbi.nlm.nih.gov

A phase I open-label clinical trial to study drug-drug interactions of Dorzagliatin and Sitagliptin in patients with type 2 diabetes and obesity. [2023]