A Study of Tirzepatide (LY3298176) in Healthy Participants and Participants With Type 2 Diabetes (T2DM)

Phase 1

Completed

Brief Summary: The main purposes of this study are to determine:

* The safety of tirzepatide and any side effects that might be associated with it.

* How much tirzepatide gets into the bloodstream and how long it takes the body to get rid of it.

* How tirzepatide affects the levels of blood sugar.

This study includes 3 parts (A, B and C). Part A involves a single dose of tirzepatide taken as a subcutaneous (SC) injection just under the skin and will be approximately 10 weeks in duration, including screening. Parts B and C involve 4 doses of tirzepatide taken once weekly (over 4 weeks) as a SC injection just under the skin and is approximately 12-14 weeks in duration, including screening. Each participant will enroll in only one part.

This study is for research purposes only, and is not intended to treat any medical condition.

Recruitment & Eligibility

Inclusion Criteria

Healthy participants (Parts A and B) and participants with T2DM diagnosed at least 1 year before enrollment (Part C)
Have a screening body mass index (BMI) of greater than 18.5 and less than or equal to 40.0 kilograms per meter squared (kg/m²), inclusive
Participants with T2DM (Part C only): have T2DM controlled with diet and exercise alone or are stable on a single oral antidiabetic medication (metformin for at least 30 days or sulfonylureas). Participants receiving sulfonylureas may participate only if this treatment is stopped for at least 6 weeks before dosing with study drug

Exclusion Criteria

Have known allergies to tirzepatide, glucagon-like peptide (GLP)-1 analogs, or related compounds
Have an abnormality in the 12-lead electrocardiogram (ECG) at screening that, in the opinion of the investigator, increases the risks associated with participating in the study
Have a history or presence of pancreatitis (history of chronic pancreatitis or idiopathic acute pancreatitis), elevation in serum amylase or lipase (greater than 2-fold the upper limit of normal [ULN]) or gastrointestinal (GI) disorder (for example, relevant esophageal reflux or gall bladder disease) or any GI disease which impacts gastric emptying (for example, gastric bypass surgery, pyloric stenosis, with the exception of appendectomy) or could be aggravated by glucagon-like peptide-1 (GLP-1) analogs or dipeptidyl peptidase (DPP)-IV inhibitors

Participants with T2DM (Part C only)

Have had more than 1 episode of severe hypoglycemia, as defined by the American Diabetes Association criteria, within 6 months before entry into the study or has a history of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms

All Study Participants (Parts B and C only)

have known allergies to tirzepatide, GLP-1 analogs, or related compounds, or acetaminophen

Arm && Interventions

Group	Intervention	Description
Placebo (Part B)	Placebo	Participants received placebo once weekly for four weeks by subcutaneous injection.
Placebo (Part A)	Placebo	Participants received single dose of placebo by subcutaneous injection.
Placebo (Part C)	Placebo	Participants received placebo once weekly for four weeks by subcutaneous injection.
Tirzepatide (Part A)	Tirzepatide	Participants received escalating single doses of either 0.25 milligram (mg) or 0.5mg or 1mg, or 2.5mg or 5mg or 8mg Tirzepatide by subcutaneous injection.
Tirzepatide (Part B)	Tirzepatide	Participants received fixed doses of either 0.5mg or 1.5mg or 4.5mg Tirzepatide once weekly for four weeks or titrated doses of 5mg, 5mg, 8mg and 10mg Tirzepatide once weekly for four weeks by subcutaneous injection.
Dulaglutide (Part B)	Dulaglutide	Participants received 1.5mg Dulaglutide once weekly for four weeks by subcutaneous injection.
Tirzepatide (Part C)	Tirzepatide	Participants received fixed doses of either 0.5mg or 5mg Tirzepatide once weekly for four weeks or titrated doses of 5mg,5mg,10mg,10mg or 5mg,5mg,10mg,15mg Tirzepatide once weekly for four weeks by subcutaneous injection

Primary Outcome Measures

Name	Time	Method
Number of Participants With One or More Serious Adverse Event(s) (SAEs)	Baseline through Day 43 (Part A) and Day 57 (Part B and C)	Number of participants with one or more SAEs considered by the investigator to be related to study drug administration. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, were reported in the Reported Adverse Events module

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide in Part A.	Predose, 8hours(h), 24h,48h,72h,96h,120h,168h,336h postdose, day 29, day 43	Area under the concentration versus time curve from zero to infinity (AUC \[0-∞\]) of Tirzepatide in Part A.
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide in Part B	Predose, 8hours(h), 24h,48h,72h,168h postdose	Area under the concentration versus time curve during 1 dosing interval (AUC \[0-τ\]) of Tirzepatide in Part B. τ equals 168 hours.
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide in Part C	Predose, 8hours(h), 24h,48h,72h,168h postdose	Area under the concentration versus time curve during 1 dosing interval (AUC \[0-τ\]) of Tirzepatide in Part C. τ equals 168 hours.
Pharmacodynamics (PD): Ratio of AUC of Glucose on Day 2 to Baseline (Part C)	Pre-glucose dose, 0.5, 1, 1.5, 2 hours post-glucose dose on Day -1 and Day 2	PD: Glucose area under the concentration versus time curve from time 0 to 2 hours (AUC\[0-2h\]) in Part C. Ratio to Baseline (Day -1) AUC (0-2h).
Pharmacodynamics (PD): Ratio of AUC of Glucose on Day 23 to Baseline (Part C)	Pre-glucose dose, 0.5, 1, 1.5, 2 hours post-glucose dose on Day -1 and Day 23	PD: Glucose area under the concentration versus time curve from time 0 to 2 hours (AUC\[0-2h\]) in Part C. Ratio to Baseline (Day -1) AUC (0-2h).

Locations (2): For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
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Singapore, Singapore
Miami Research Associates
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South Miami, Florida, United States