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  1. Medical Information Right
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  3. Foundayo (orforglipron) tablet Right
  4. Does Foundayo™ (orforglipron) lead to changes in pancreatic amylase and lipase enzymes?
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Foundayo ™ (orforglipron) tablet

0.8 mg / 2.5 mg / 5.5 mg / 9 mg / 14.5 mg / 17.2 mg

Full Prescribing Information

This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.

Does Foundayo™ (orforglipron) lead to changes in pancreatic amylase and lipase enzymes?

In ATTAIN-1 and -2, orforglipron increased mean serum amylase and lipase, with mean values remaining within the normal range. In the absence of other pancreatitis signs and symptoms, elevations in these enzymes alone are not predictive of pancreatitis.

US_cFAQ_OFG506B_AMYLASE_LIPASE_WM
US_cFAQ_OFG506B_AMYLASE_LIPASE_WMen-US

Content Overview 

Prescribing Information Related to Amylase and Lipase Elevations

Were Pancreatic Amylase and Lipase Enzymes Elevated During the Clinical Trials? 

Clinical Considerations for Patients Experiencing Amylase and Lipase Elevations

See important safety information, including boxed warning, in the attached prescribing information.

Prescribing Information Related to Amylase and Lipase Elevations

In a pool of ATTAIN-1 and ATTAIN-2, mean increases from baseline in serum pancreatic amylase and serum lipase concentrations were

  • 16% to 20% and 26% to 31% with orforglipron, and 
  • 3% and 4% with placebo, respectively.1

The clinical significance of elevations in pancreatic amylase or lipase with orforglipron is unknown in the absence of other signs and symptoms of pancreatitis.1

Were Pancreatic Amylase and Lipase Enzymes Elevated During the Clinical Trials? 

ATTAIN-1 and ATTAIN-2 were randomized, double-blind, placebo-controlled trials evaluating the efficacy and safety of orforglipron adults with obesity or overweight. ATTAIN-1 enrolled participants without type 2 diabetes (T2D) and ATTAIN-2 enrolled participants with T2D.2,3

These studies compared an investigational orforglipron capsule formulation with placebo during 72 weeks, plus a 2-week off-drug follow-up.2,3

This response presents safety data from the investigational orforglipron capsule formulation (1 mg, 3 mg, 6 mg, 12 mg, 24 mg, and 36 mg) shown as equivalent doses of once daily orforglipron tablets (0.8 mg, 2.5 mg, 5.5 mg, 9 mg, 14.5 mg, and 17.2 mg) approved in the United States.1-3

To assess the effect of orforglipron on pancreatic enzyme levels, each participant had measurements of pancreatic amylase and lipase levels at

  • baseline, and
  • weeks 12, 24, and 72.2,4

Change from baseline in pancreatic amylase and lipase levels at week 72 in the ATTAIN-1 and ATTAIN-2 trials are presented in 

  • Change From Baseline at Week 72 in Pancreatic Amylase Levels in ATTAIN-1 and -2, and 
  • Change From Baseline at Week 72 in Lipase Levels in ATTAIN-1 and -2.

Compared with baseline, mean serum levels of pancreatic amylase and lipase were higher for participants in each orforglipron group at week 72 compared with placebo, but remained below 100 U/L. However, no asymptomatic cases of pancreatic enzyme elevations were confirmed by adjudication as pancreatitis in the orforglipron groups.4

Therefore, during ATTAIN-1 and ATTAIN-2, further diagnostic follow-up of cases in participants with asymptomatic elevation of pancreatic enzymes (lipase and/or pancreatic amylase ≥3x upper limit of normal [ULN]) was not mandatory and was performed based on the investigator’s clinical judgment and assessment of the participant’s overall clinical condition.2,4

Mean serum levels of pancreatic amylase and lipase for participants treated with orforglipron increased from week 0 to week 12 and plateaued through week 72 with all mean values remaining below 100 U/L.4

Change From Baseline at Week 72 in Pancreatic Amylase Levels in ATTAIN-1 and -21-3

Pancreatic Amylase Levels in ATTAIN-1a

OFG 5.5 mg
(N=723)

OFG 9 mg 
(N=724)

OFG 17.2 mg
(N=728)

PBO
(N=948)

Baseline, U/L

23.2

23.3

23.2

23.5

Week 72, U/L

26.7

26.8

26.7

23.6

Percent change from baseline at week 72, %

14.1

14.4

14.2

1.1

Pancreatic Amylase Levels in ATTAIN-2a

OFG 5.5 mg
(N=328)

OFG 9 mg 
(N=331)

OFG 17.2 mg 
(N=321)

PBO 
(N=628)

Baseline, U/L

22.7

23.0 

23.1

23.6

Week 72, U/L

27.8

30.3

30.3

24.6

Percent change from baseline at week 72, %

20.3

31.4

31.4

6.5

Abbreviations: OFG = orforglipron; PBO = placebo. 

Note: Data presented are model-based estimate analyzed with log-transformation. 

aNormal amylase range is 3 – 46 U/L for male and female participants. 

Change From Baseline at Week 72 in Lipase Levels in ATTAIN-1 and -21-3

Lipase Levels in ATTAIN-1a

OFG 5.5 mg
(N=723)

OFG 9 mg 
(N=724)

OFG 17.2 mg
(N=728)

PBO
(N=948)

Baseline, U/L

28.0

29.9

28.7

28.7

Week 72, U/L

36.9

37.9

37.1

29.9

Percent change from baseline at week 72, % 

28.1

31.7

28.8

4.0

Lipase Levels in ATTAIN-2b

OFG 5.5 mg
(N=328)

OFG 9 mg 
(N=331)

OFG 17.2 mg 
(N=321)

PBO 
(N=628)

Baseline, U/L

36.1

35.7

37.2

36.5

Week 72, U/L

44.2

47.3

47.0

37.7

Percent change from baseline at week 72, %

21.5

29.8

29.0

3.6

Abbreviations: OFG = orforglipron; PBO = placebo. 

Note: Data presented are model-based estimate analyzed with log-transformation. 

aNormal lipase levels were 0-100 U/L in male and female participants. 

bNormal lipase levels were 0-120 U/L in male and female participants. 

Serial measures of pancreatic enzymes have limited clinical value for predicting episodes of acute pancreatitis in asymptomatic patients.5-7

Back to Content Overview .

Clinical Considerations for Patients Experiencing Amylase and Lipase Elevations

Acute pancreatitis has been reported in patients treated with orforglipron. Fatal and non-fatal hemorrhagic or necrotizing pancreatitis have been observed in patients treated with glucagon-like peptide-1 receptor agonists.1

After initiation of orforglipron, observe patients carefully for signs and symptoms of acute pancreatitis, which may include persistent or severe abdominal pain (sometimes radiating to the back) and which may or may not be accompanied by nausea or vomiting.1 

If pancreatitis is suspected, discontinue orforglipron and initiate appropriate management.1

In a pool of ATTAIN-1 and ATTAIN-2, 6 events of acute pancreatitis were confirmed by adjudication in 6 orforglipron-treated patients (0.14 patients per 100 years of exposure) versus 2 events in 1 placebo-treated patient (0.04 patients per 100 years of exposure).4

Eli Lilly and Company cannot provide treatment recommendations for the initiation, continuation, discontinuation, or reinitiation of orforglipron in patients with

  • elevated amylase or lipase levels, or 
  • amylase or lipase levels that have returned to normal. 

In formulating an assessment and approach, the health care practitioner may consider 

  • the patient’s prior medical history and concomitant medications, and
  • other individual factors.

The health care practitioner should consider potential risks and benefits of treatment options and monitor appropriately.

Back to Content Overview .

Enclosed Prescribing Information

FOUNDAYO™ (orforglipron) tablets, for oral use, Lilly

References

The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).

1Foundayo [package insert]. Indianapolis, IN: Eli Lilly and Company; 2026.

2Wharton S, Aronne LJ, Stefanski A, et al; ATTAIN-1 Trial Investigators. Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment. N Engl J Med. 2025;393(18):1796-1806. https://doi.org/10.1056/NEJMoa2511774

3Horn DB, Ryan DH, Giljanovic Kis S, et al; ATTAIN-2 Trial Investigators. Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. Lancet. 2025;406(10522):2927-2944. https://doi.org/10.1016/S0140-6736(25)02165-8

4Data on file, Eli Lilly and Company and/or one of its subsidiaries.

5Nauck MA, Frossard JL, Barkin JS, et al. Assessment of pancreas safety in the development program of once-weekly GLP-1 receptor agonist dulaglutide. Diabetes Care. 2017;40(5):647-654. http://dx.doi.org/10.2337/dc16-0984

6Steinberg WM, Rosenstock J, Wadden TA, et al. Impact of liraglutide on amylase, lipase, and acute pancreatitis in participants with overweight/obesity and normoglycemia, prediabetes, or type 2 diabetes: secondary analyses of pooled data from the SCALE clinical development program. Diabetes Care. 2017;40(7):839-848. https://doi.org/10.2337/dc16-2684

7Steinberg WM, Buse JB, Ghorbani MLM, et al; the LEADER Trial Investigators. Amylase, lipase, and acute pancreatitis in people with type 2 diabetes treated with liraglutide: results from the LEADER randomized trial. Diabetes Care. 2017;40(7):966-972. https://doi.org/10.2337/dc16-2747

Date of Last Review: April 03, 2026

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