Diabetes Medications for Type 2 Diabetes

Not currently recruiting at 2 trial locations

Overseen By Rita Basu, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Alabama at Birmingham

Must not be taking: Insulin, SGLT2 inhibitors

Disqualifiers: Unstable diabetic retinopathy, macrovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests three treatments to determine their effectiveness in controlling high blood sugar at night for people with type 2 diabetes. Participants will be randomly assigned to take insulin, metformin, or dorzagliatin (an experimental treatment) for 8 weeks. The goal is to identify which treatment best maintains steady blood sugar levels overnight. The trial seeks individuals who have managed type 2 diabetes with lifestyle changes or certain medications but have not used insulin. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to the development of potentially groundbreaking treatments.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that dorzagliatin, a newer diabetes medication, is generally safe but can cause some side effects. In one study, participants taking dorzagliatin experienced more side effects overall compared to those not taking it, though serious side effects were rare. Another study found that dorzagliatin effectively lowered blood sugar with fewer side effects than other treatments.

Insulin glargine and metformin are both well-known diabetes treatments. Insulin glargine is widely used and usually well-tolerated, helping control blood sugar by supplementing or replacing the body's insulin. Metformin is also a common treatment for type 2 diabetes, generally safe but may cause stomach issues, especially at the start of treatment.

Overall, while dorzagliatin appears promising, it is newer and might have more side effects compared to well-established medications like insulin glargine and metformin. Participants should consider these factors when deciding to join this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Dorzagliatin is unique because it targets the root cause of type 2 diabetes by regulating blood sugar levels through the activation of a protein called glucokinase. Unlike standard treatments like Metformin or Insulin Glargine, which primarily focus on managing blood sugar levels, Dorzagliatin works by enhancing the body’s natural ability to regulate glucose. Researchers are excited about Dorzagliatin because it offers a novel approach that could potentially improve blood sugar control with fewer side effects, providing a new option for people with type 2 diabetes.

What evidence suggests that this trial's treatments could be effective for type 2 diabetes?

Research has shown that insulin glargine, one of the treatments in this trial, effectively lowers blood sugar and is commonly used to treat type 2 diabetes. Studies have found that metformin, another treatment option in this trial, can also lower blood sugar and improve insulin utilization. Dorzagliatin, the experimental treatment being tested, significantly reduces blood sugar and enhances insulin use. It also helps lower glycated hemoglobin levels, indicating long-term blood sugar control. Each of these treatments has proven effective in managing blood sugar in people with type 2 diabetes. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Dorzagliatin
• Insulin Glargine
• Metformin

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.

How Is the Trial Designed?

Group I: Dorzagliatin Experimental Treatment 1 Intervention

Group II: Metformin Active Control 1 Intervention

Group III: Insulin Glargine 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+

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

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]

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]

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]

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]

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 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 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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9727304/

Efficacy and safety of dorzagliatin for type 2 diabetes mellitus Dorzagliatin was effective in lowering glycemia, reducing insulin resistance and improving islet ß-cells function without affecting blood pressure, LDL-C, and ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149291823003569

Review Dorzagliatin for Type 2 Diabetes Mellitus Overall, the meta-analysis showed that dorzagliatin remarkably reduced glycated hemoglobin levels versus placebo by 0.66%. The results of the meta-analysis ...

3. journals.lww.com journals.lww.com/md-journal/fulltext/2024/02230/efficacy_and_safety_of_dorzagliatin,_a_novel.8.aspx

Efficacy and safety of dorzagliatin, a novel glucokinase... Compared with placebo group, dorzagliatin significantly reduced blood glucose levels as well as enhanced insulin resistance. In terms of safety, ...

4. diabetesjournals.org diabetesjournals.org/diabetes/article/doi/10.2337/db24-1130/163364/Effects-of-Dorzagliatin-a-Glucokinase-Activator-on

Effects of Dorzagliatin, a Glucokinase Activator, on α- and β ... Dorzagliatin significantly increased second-phase insulin secretion rate and β-cell glucose sensitivity by 1.3-fold compared with placebo in IGT ...

5. nature.com nature.com/articles/s41591-022-01803-5

Dorzagliatin add-on therapy to metformin in patients with ... Dorzagliatin improved glycemic control when administered orally for 24 weeks at a dose of 75 mg twice daily (BID) to drug-naive patients with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06263348

A Post-Marketing Safety Study of Dorzagliatin in Patients ... The primary objective of this study is to evaluate the long-term safety of Dorzagliatin in a larger population of type 2 diabetes mellitus patients by ...