Oral Anti-Diabetes Drugs vs Insulin for Diabetes

Recruiting at 2 trial locations

Overseen By Maya Fayfman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Emory University

Must be taking: Oral antidiabetics

Must not be taking: Corticosteroids

Disqualifiers: Type 1 diabetes, Renal impairment, others

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

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 10 days

260 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized controlled clinical trial will assess whether continuation of home oral antidiabetic agents during hospitalization can be used as a safe and effective alternative to insulin therapy in the management of diabetes in the hospital. The primary outcome of the study is to determine differences in glycemic control as measured by mean daily blood glucose concentration between oral antidiabetic medications and basal bolus therapy in hospitalized patients with type 2 diabetes (T2D).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it seems to focus on continuing oral antidiabetic drugs during hospitalization. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of oral anti-diabetes drugs for diabetes?

Research shows that oral anti-diabetes drugs (OADs) can help improve blood sugar control in people with type 2 diabetes. Studies in Japan and China have observed that these drugs are commonly used and can be effective in managing blood sugar levels. ^{1 2 3 4 5}

Are oral antidiabetic drugs generally safe for humans?

Oral antidiabetic drugs (OADs) like metformin and sulfonylureas have a well-established safety record, though metformin can cause stomach discomfort and sulfonylureas may lead to low blood sugar and weight gain. Some newer drugs, like thiazolidinediones, have raised concerns about heart-related issues, but alpha-glucosidase inhibitors are considered safe, despite some tolerability issues. ^{2 6 7 8 9}

How do oral anti-diabetes drugs differ from insulin for diabetes treatment?

Oral anti-diabetes drugs (OADs) are taken by mouth and work in various ways, such as reducing sugar production in the liver or increasing insulin sensitivity, while insulin is injected and directly provides the hormone needed to regulate blood sugar. OADs can be used alone or in combination with other drugs, but many patients eventually need insulin to maintain blood sugar control. ^{2 10 11 12 13}

Research Team

Maya Fayfman, MD

Principal Investigator

Emory University

Eligibility Criteria

This trial is for adults aged 18-80 with type 2 diabetes, admitted to general medicine and surgery services, not critically ill or pregnant. Participants must have a blood glucose under 250 mg/dl, HbA1c below 10%, be on oral anti-diabetes drugs (OADs), and have functioning kidneys. Those with type 1 diabetes, severe COVID-19, or on steroids can't join.

Inclusion Criteria

I have type 2 diabetes and am taking oral diabetes medications.

I am between 18 and 80 years old and admitted for general medical or surgical care.

HbA1c <10%

Exclusion Criteria

I am expected not to eat or drink for more than 24-48 hours after being admitted or after surgery.

Laboratory evidence of diabetic ketoacidosis

I have never been diagnosed with diabetes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants continue their home oral antidiabetic agents or switch to basal bolus insulin therapy during hospitalization

Up to 10 days

Daily monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, including hospital complications and re-admissions

30 days

Treatment Details

Interventions

• Oral Anti-diabetes Drugs

Trial Overview The study tests if continuing home oral anti-diabetes drugs in the hospital is as effective as insulin therapy for managing diabetes. It compares daily blood sugar control using these drugs versus basal bolus insulin therapy in hospitalized patients.

Participant Groups

Group I: Oral Anti-diabetes Drugs (OADs) alone Experimental Treatment 3 Interventions

OADs will be continued at same outpatient dosage unless contraindicated

Group II: Basal bolus insulin Active Control 3 Interventions

Basal insulin with glargine or detemir and rapid-acting insulin (lispro/aspart) will be used as per the hospital formulary. OADs and non-insulin injectable antidiabetic medication will be discontinued on admission.

Oral Anti-diabetes Drugs is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Oral Anti-diabetes Drugs for:

• Type 2 diabetes

Approved in United States as Oral Anti-diabetes Drugs for:

• Type 2 diabetes

Approved in Canada as Oral Anti-diabetes Drugs for:

• Type 2 diabetes

Approved in Japan as Oral Anti-diabetes Drugs for:

• Type 2 diabetes

Approved in China as Oral Anti-diabetes Drugs for:

• Type 2 diabetes

Approved in Switzerland as Oral Anti-diabetes Drugs for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

Over a 10-year period from 2002 to 2011, the use of sulfonylureas (SUs) for monotherapy in type 2 diabetes treatment significantly decreased, while biguanides (BGs) saw an increase in both mono- and combination therapies.

The introduction of DPP-4 inhibitors in 2009 led to their rise as the third most commonly prescribed oral antidiabetic drug by 2011, contributing to improved glycemic control as indicated by a reduction in average glycated hemoglobin levels from 7.5% to 7.1%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in oral antidiabetic prescriptions and improved glycemic control during the years 2002-2011 in Japan (JDDM32). Oishi, M., Yamazaki, K., Okuguchi, F., et al.[2022]

In a study of type 2 diabetes patients with poor glycemic control despite insulin therapy, adding tofogliflozin significantly improved HbA1c levels, reducing them by -1.0% compared to a slight decrease in the insulin-only group.

Tofogliflozin not only helped lower HbA1c but also reduced the total daily insulin dose and weight in patients, indicating it may be a safe and effective add-on therapy for better diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Combined Tofogliflozin and Glargine, Tofogliflozin Added to Insulin, and Insulin Dose-Increase Therapy in Uncontrolled Type 2 Diabetes. Suzuki, K., Mitsuma, Y., Sato, T., et al.[2022]

In a study of 4627 patients with type 2 diabetes, those with moderate or poor glycemic control were significantly more likely to change their oral antidiabetic treatment patterns, such as switching or augmenting therapy, compared to those with good control.

Men generally had worse glycemic control at the start of treatment, and younger patients were more likely to modify their therapy, indicating that initial control levels and demographics play a crucial role in treatment adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycemic control and the first use of oral antidiabetic agents among patients with type 2 diabetes mellitus. Mitchell, BD., Eby, EL., Lage, MJ.[2013]

In a study of 9,872 older adults with type 2 diabetes in China, insulin secretagogues, particularly sulfonylureas and glinides, were the most commonly used oral antidiabetes drugs, with dual combination therapy being the prevalent treatment approach.

Older patients (≥65 years) often struggled with glycemic control, especially those on triple or more combination treatments, indicating a need for more comprehensive treatment strategies to improve their diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Patterns and Glycemic Control in Older Adults with Type 2 Diabetes Mellitus Receiving Only Oral Antidiabetes Drugs in China. Zhang, L., Ji, L., Guo, L., et al.[2022]

In a study of 9,872 outpatients with type 2 diabetes in China, insulin secretagogues were the most commonly used oral anti-diabetic drugs, with 70.2% of patients on these medications, indicating a preference for this class of drugs in managing diabetes.

The study found that dual-drug combination therapy was more prevalent (45.4%) than monotherapy (35.8%), and patients on sulfonylureas or glinides were more likely to frequently change their treatment due to perceived poor effectiveness, highlighting challenges in diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

China type 2 diabetes treatment status survey of treatment pattern of oral drugs users Ji, L., Lu, J., Weng, J., et al.[2016]

Pharmacogenetic factors, such as genetic variations in drug-metabolizing enzymes, can significantly influence the effectiveness and side effects of oral antidiabetic drugs (OADs) in patients with type 2 diabetes.

While some drug-drug interactions among OADs exist, they currently do not appear to have major clinical consequences, highlighting the need for more extensive studies in diverse patient populations to better understand these interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral antidiabetic drug metabolism: pharmacogenomics and drug interactions. Holstein, A., Beil, W.[2019]

In a study of 2396 patients, vildagliptin and pioglitazone/rosiglitazone showed similar overall adverse drug events, indicating that both medications are comparably safe for treating Type 2 Diabetes Mellitus (T2DM).

However, pioglitazone/rosiglitazone was associated with significantly lower dizziness compared to vildagliptin, while rosiglitazone specifically led to higher rates of weight gain and peripheral edema, suggesting the need for further investigation into these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug effects observed with vildagliptin versus pioglitazone or rosiglitazone in the treatment of patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Bundhun, PK., Janoo, G., Teeluck, AR., et al.[2018]

Insulin-dependent oral antidiabetic agents like metformin, sulfonylureas, and gliptins are generally safe but have limitations in maintaining long-term blood glucose control, with no single drug providing stable control for years.

Metformin can cause gastrointestinal discomfort, while sulfonylureas carry risks of hypoglycemia and weight gain; additionally, pioglitazone is linked to serious side effects such as bladder cancer and heart failure, highlighting the need for careful patient monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Limitations of insulin-dependent drugs in the treatment of type 2 diabetes mellitus]. Valerón, PF., de Pablos-Velasco, PL.[2018]

Biguanides and sulfonylureas, introduced in the 1950s, remain widely used for diabetes management, with well-defined safety and tolerability profiles, while newer agents like thiazolidinediones have raised concerns about potential side effects such as heart failure and hepatotoxicity.

Rapid-acting non-sulfonylurea secretagogues may offer a safer alternative for certain patients, particularly those with renal impairment, and alpha-glucosidase inhibitors like acarbose have a strong safety record, although their use is limited by tolerability issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative safety of newer oral antidiabetic drugs. Krentz, AJ.[2022]

Metformin is currently the recommended first-line oral antidiabetic drug for type 2 diabetes due to its effective blood glucose control and better safety profile compared to earlier drugs like sulfonylureas and phenformin.

Newer classes of oral antidiabetic drugs, such as sodium-glucose co-transporter 2 inhibitors and G-protein-coupled receptor agonists, are being developed with novel mechanisms of action, but rigorous safety evaluations are essential to ensure they do not have the adverse effects seen in previous generations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving therapeutic options for type 2 diabetes mellitus: an overview. Guthrie, RM.[2013]

Pharmacological treatments, including various classes of oral antidiabetic drugs, are essential for effective blood glucose control in type 2 diabetes, alongside dietary and lifestyle changes.

Different classes of oral antidiabetic drugs work through unique mechanisms, such as reducing glucose production, delaying carbohydrate absorption, and enhancing insulin sensitivity, allowing for potential synergistic effects when combined for better blood glucose management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Repaglinide in combination therapy in type 2 diabetes]. Moses, R.[2018]

A study of 71,988 patients with Type 2 diabetes showed that those starting insulin therapy after using 1 or 2 oral antidiabetes drugs (OADs) had higher treatment discontinuation rates and less A1c reduction compared to those who had used 3 or more OADs, indicating that more OADs before insulin may lead to better outcomes.

All groups experienced significant improvements in glycemic control and reduced healthcare costs after initiating insulin therapy, highlighting the importance of timely insulin initiation for patients not achieving adequate control with OADs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health Outcomes Associated with Initiation of Basal Insulin After 1, 2, or ≥ 3 Oral Antidiabetes Drug(s) Among Managed Care Patients with Type 2 Diabetes. Levin, PA., Zhou, S., Gill, J., et al.[2023]

A 6-month course of insulin therapy resulted in significantly better long-term glycemic control over 5 years compared to oral antidiabetic drugs (OADs), with lower A1C levels (6.49% vs 7.72%).

The insulin group also had a higher remission rate from diabetes (27.3% vs 5.9%), indicating that insulin therapy may be more effective in achieving sustained glycemic control and potential remission in newly diagnosed patients with severe hyperglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term glycemic control after 6 months of basal insulin therapy. Chen, HS., Wu, TE., Kuo, CS.[2022]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Changes in oral antidiabetic prescriptions and improved glycemic control during the years 2002-2011 in Japan (JDDM32). [2022]

2. Canada pubmed.ncbi.nlm.nih.gov

Comparison of Combined Tofogliflozin and Glargine, Tofogliflozin Added to Insulin, and Insulin Dose-Increase Therapy in Uncontrolled Type 2 Diabetes. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Glycemic control and the first use of oral antidiabetic agents among patients with type 2 diabetes mellitus. [2013]

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

Treatment Patterns and Glycemic Control in Older Adults with Type 2 Diabetes Mellitus Receiving Only Oral Antidiabetes Drugs in China. [2022]

5. Australia pubmed.ncbi.nlm.nih.gov

China type 2 diabetes treatment status survey of treatment pattern of oral drugs users [2016]

6. England pubmed.ncbi.nlm.nih.gov

Oral antidiabetic drug metabolism: pharmacogenomics and drug interactions. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Adverse drug effects observed with vildagliptin versus pioglitazone or rosiglitazone in the treatment of patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. [2018]

8. Spain pubmed.ncbi.nlm.nih.gov

[Limitations of insulin-dependent drugs in the treatment of type 2 diabetes mellitus]. [2018]

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

Comparative safety of newer oral antidiabetic drugs. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Evolving therapeutic options for type 2 diabetes mellitus: an overview. [2013]

11. France pubmed.ncbi.nlm.nih.gov

[Repaglinide in combination therapy in type 2 diabetes]. [2018]

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

Health Outcomes Associated with Initiation of Basal Insulin After 1, 2, or ≥ 3 Oral Antidiabetes Drug(s) Among Managed Care Patients with Type 2 Diabetes. [2023]

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

Long-term glycemic control after 6 months of basal insulin therapy. [2022]