Phase II Study of Switching From Dulaglutide to PG-102(MG12) in Type 2 Diabetes Mellitus

A Randomized, Open-Label, Multicenter, Active-Controlled Phase 2 Study to Evaluate the Efficacy and Safety of Switching From Once-Weekly Dulaglutide to Once-Monthly PG-102(MG12) in Patients With Type 2 Diabetes Mellitus Receiving Stable Dulaglutide Therapy

This is a randomized, open-label, multi-center, active-controlled Phase 2 clinical trial to evaluate the efficacy and safety of switching from once-weekly dulaglutide to PG-102(MG12) in patients with type 2 diabetes mellitus receiving stable dulaglutide therapy.

The treatment period is 32 weeks, with an additional 4-week safety follow-up. The primary endpoint is the change in HbA1c(%) from baseline at Week 32.

Participants will be randomized 1:1:1 to three treatment arms: two PG-102(MG12) dose groups and one active-control group (dulaglutide), over a 32-week treatment period , with an additional 4-week safety follow-up.

PG-102(MG12) will be administered with a dose titration schedule: once weekly for the first 4weeks, once every 2 weeks for the following 4 weeks, and once every 4 weeks for the remaining 24 weeks.

The dulaglutide control group will continue their current maintenance dose once weekly per label.

Inclusion Criteria:

1. Adults aged 19 to 75 years who provide informed consent.
2. Diagnosed with type 2 diabetes for at least 6 months prior to screening.
3. Stable on dulaglutide therapy (0.75 or 1.5 mg) for at least 12 weeks prior to screening, with dose and dosing interval maintained unchanged for 8 weeks prior to enrollment.
4. HbA1c ≤ 7.5% at screening.
5. If receiving oral anti-diabetic drugs (OADs), on a stable dose for at least 90 days prior to screening.
6. BMI between 18.5 kg/m² and 30.0 kg/m².

Exclusion Criteria:

1. Received any investigational medicinal product within 30 days prior to screening, or within 5 half-lives of the product if known (whichever is longer).
2. History of hypersensitivity or severe adverse reactions to GLP-1RA, GLP-2 agents, the investigational product, or its components.
3. Type 1 diabetes, special forms of diabetes (e.g., monogenic, post-pancreatectomy, steroid-induced), or history of DKA or HHS within 6 months prior to screening
4. Severe gastrointestinal disorders affecting gastric emptying (e.g., gastroparesis, inflammatory bowel disease, gastric/duodenal ulcer, intestinal obstruction) or history of related surgery within the past year (e.g., sleeve gastrectomy, biliopancreatic diversion, jejunal/ileal bypass).
5. Uncontrolled hypertension (systolic ≥180 mmHg or diastolic ≥110 mmHg) or severe hypertriglyceridemia (fasting triglycerides ≥500 mg/dL) despite appropriate treatment. Patients may be enrolled if these conditions are adequately controlled during screening.
6. NYHA Class III or IV heart failure; acute coronary syndrome (including MI), unstable angina, clinically significant CAD (CCS Class III-IV), CABG or emergent PCI, TIA, or cerebrovascular accident within the past 6 months. Patients may be enrolled if the event occurred >6 months ago and is considered resolved or stable.
7. Active pancreatitis, history of recurrent or severe pancreatitis, or clinically significant gallbladder disease (e.g., cholecystitis, complications from gallstones) that is unresolved or at risk of recurrence.
8. Active malignancy or history of malignancy treatment within the past 5 years. Exceptions: completely cured basal cell carcinoma, cervical carcinoma in situ, or other cured malignancies with no risk of recurrence as judged by the investigator.
9. Personal or family history (first-degree relatives) of MEN type 2 or thyroid C-cell carcinoma (e.g., MTC). Exception: surgically cured simple thyroid nodules or benign non-C-cell thyroid conditions (e.g., thyroid adenoma, thyroid dysfunction).
10. Active infectious disease (e.g., active TB, active viral hepatitis, HIV), or confirmed HBsAg-positive, HCV RNA-positive, or HIV infection, unless documented to be completely cured or currently inactive.
11. History of hospitalization or emergency treatment for moderate or severe depressive disorder, bipolar disorder, or schizophrenia spectrum disorder within the past year. Exception: patients whose symptoms are currently stable under appropriate treatment and deemed safe to participate as assessed by the investigator.
12. Therapeutic use of systemic corticosteroids for more than 14 days within 90 days prior to screening. Exception: short-term use (≤10 days) or non-absorbable topical, inhaled, intra-articular, or dermatological formulations.
13. Diagnosis of or clinically suspected alcohol or drug abuse or dependence within 90 days prior to screening.
14. AST or ALT >3× ULN or total bilirubin >2× ULN at screening. Exception: transient elevations confirmed to have normalized or to be stable on repeat testing.
15. Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m² calculated by CKD-EPI equation.
16. Moderate or severe hepatic impairment (Child-Pugh Grade B or above) or currently active drug-induced liver disease. Exception: history of drug-induced liver disease with complete recovery and stable liver function tests (AST, ALT, total bilirubin) within normal range.

"17. Severe or active diabetic complications, including:

• Proliferative diabetic retinopathy currently receiving or requiring treatment (laser, vitrectomy, anti-VEGF, or steroid injections) within the past 3 months or planned treatment. (Non-proliferative or stable retinopathy is permitted with fundus examination at screening and regular follow-up.)

• Diabetic nephropathy with overt proteinuria (≥300 mg/day) or eGFR <45 mL/min/1.73 m²

• Severe diabetic neuropathy with uncontrolled pain despite optimized pharmacotherapy (e.g., antidepressants, gabapentinoids, analgesics) for ≥3 months, requiring continuous use of opioid or multiple combination analgesics.

• Exception: patients with past complications that are currently stable and deemed safe to participate as assessed by the investigator." 18. Fertile women or fertile men (including those with fertile female partners) who do not agree to use dual contraception or abstinence from the time of written consent until 90 days after the last dose of investigational product. (Fertile women must have a negative serum pregnancy test during screening prior to study entry).

  19. Currently pregnant or breastfeeding, or planning pregnancy during the study period or within 90 days after the last dose of investigational product.

  20. Previous experience of persistent or recurrent vomiting or severe diarrhea requiring hospitalization, emergency treatment, or drug discontinuation following GLP-1 receptor agonist or GLP-2 analogue administration, or history of intestinal obstruction.

  21. Patients who required dose reduction of dulaglutide due to intolerance and subsequently failed re-escalation to the previous dose. Exception: patients assessed by the investigator as currently maintaining stable treatment at the reduced dose.

  22. History of or planned use of prohibited concomitant medications within 90 days prior to screening or during the study period. Exception: short-term use (≤14 days) for therapeutic necessity with no anticipated pharmacokinetic or pharmacodynamic interaction with the investigational product as judged by the investigator.

  23. Use of insulin for diabetes management during the 1 year prior to screening. Exception: acute short-term use (≤14 days) during hospitalization or perioperative periods.

  24. Patients deemed inappropriate for study participation by the investigator based on safety, compliance, or medical judgment (considering physical examination, baseline test results, medical history, etc.).

  25. Self-reported body weight change of >5% within 12 weeks (90 days) prior to screening.

  26. History of untreatable colorectal polyps. 27. Presence of factors that may affect IGF-1 measurement, such as growth hormone (GH) injections.