Trulicity ® (dulaglutid) injektion

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Denna information är endast avsedd för sjukvårdspersonal verksam i Sverige och som svar på din fråga. Informationen nedan är på engelska

Finns det risk för Pankreatit med Trulicity® (dulaglutid)?

Akut pankreatit har rapporterats i samband med dulaglutid i kliniska prövningar. Användningen av GLP -1 -receptoragonister har förknippats med en risk att utveckla akut pankreatit.

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How many cases of pancreatitis were reported in the dulaglutide clinical program?

The pancreatic safety of dulaglutide was assessed in an integrated analysis of 4 phase 2 and 5 phase 3 studies in 6005 patients with Type 2 Diabetes (T2D).1 

A blinded external adjudication committee evaluated and assessed the

  • investigator-reported adverse events (AEs) of pancreatitis
  • asymptomatic, confirmed increases in at least 1 pancreatic enzyme of ≥ 3 times the upper limit normal (ULN), and
  • AEs of severe or serious abdominal pain without a known etiology.1

The incidence of acute pancreatitis was

  • 0.07 % for dulaglutide compared to
  • 0.14 % for placebo. 

Acute pancreatitis and pancreatitis have also been reported in the post-marketing setting.2

In the integrated analysis, a total of 203 events were adjudicated in 151 patients. Pancreatitis was confirmed in 9 patients, of which 

  • 5 patients were treated with dulaglutide
  • 3 patients were treated with sitagliptin, and
  • 1 patient was receiving placebo.1

All 5 patients with confirmed pancreatitis who were being treated with dulaglutide had elevated pancreatic enzymes at baseline prior to initiation of dulaglutide.1

Acute Pancreatitis

Of the 9 patients with adjudicated pancreatitis, 7 patients had acute pancreatitis including

  • 3 patients treated with dulaglutide
  • 3 patients treated with sitagliptin, and
  • 1 patient receiving placebo.1

The type of pancreatitis was not determined in 1 of the 3 patients receiving dulaglutide. For data analysis, this case was categorized as “acute.” In the assessment of risk factors for acute pancreatitis, this patient had cholelithiasis.1

The exposure-adjusted incidence rates of acute pancreatitis were

  • 0.85 patients/1000 patient-years in the dulaglutide group
  • 4.71 patients/1000 patient-years in the sitagliptin group, and
  • 3.52 patients/1000 patient-years in the placebo group.1

Chronic Pancreatitis

There were 2 reported events of chronic pancreatitis in patients receiving dulaglutide.

The exposure-adjusted incidence rate of chronic pancreatitis was 0.57 patients/1000 patient-years in the dulaglutide group.1

Pancreatitis in the REWIND Study

The REWIND study was an event-driven, randomized, double-blind, phase 3 study evaluating once-weekly dulaglutide 1.5 mg treatment compared with placebo when added to standard of care on a composite endpoint of major adverse cardiovascular events (death due to cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke) (MACE-3) in adults with T2D and established cardiovascular disease and/or risk factors.3,4

The instance of pancreatitis, did not differ significantly between the dulaglutide and placebo treatment groups (Acute Pancreatitis in the Dulaglutide REWIND Study).4

Acute Pancreatitis in the Dulaglutide REWIND Study4

 

Dulaglutide
(n=4949)

Placebo
(n=4952)

P Value

Acute pancreatitisa

23

13

0.11

Imaging and enzymesb

4

3

0.71

Imaging, enzymes, and symptomsc

4

3

0.71

Abbreviation: REWIND = Researching cardiovascular Events with a Weekly INcretin in Diabetes.

aBased on the first occurrence of acute pancreatitis diagnosed on the basis of at least 2 of 3 diagnostic criteria which include symptoms, elevated pancreatic enzymes, and an abnormal pancreatic image.

bSubset of patients with acute pancreatitis who also had both elevated pancreatic enzymes and an abnormal pancreatic image.

cSubset of patients with acute pancreatitis who had elevated pancreatic enzymes, an abnormal pancreatic image, and symptoms.

Pancreatitis in the AWARD-11 Study

The AWARD-11 trial was a phase 3, randomized, double-blind, active-controlled, parallel-arm study that assessed the efficacy and safety of dulaglutide 3.0 mg and 4.5 mg compared with dulaglutide 1.5 mg in patients with inadequately controlled T2D on concomitant metformin therapy.5

6 patients were reported with adjudication-confirmed acute pancreatitis including

  • 1 patient, 0.2%, in the dulaglutide 1.5 mg group
  • 2 patients, 0.3%, in the dulaglutide 3.0 mg group, and
  • 3 patients, 0.5%, in the dulaglutide 4.5 mg  group.6

All cases were acute and were reported as mild in severity with no pancreatic complications.6

One patient who was assigned to dulaglutide 4.5 mg, with a confirmed case of acute pancreatitis, had a previously undisclosed history of pancreatitis and would have been excluded from enrollment had this been known at the time of screening.6

References

1Nauck 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

2Trulicity [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

3Gerstein HC, Colhoun HM, Dagenais GR, et al; REWIND Trial Investigators. Design and baseline characteristics of participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide. Diabetes Obes Metab. 2018;20(1):42-49. https://doi.org/10.1111/dom.13028

4Gerstein HC, Colhoun HM, Dagenais GR, et al; REWIND Investigators. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019;394(10193):121-130. https://doi.org/10.1016/S0140-6736(19)31149-3

5Frias JP, Nevárez Ruiz L, Li YG, et al. Efficacy and safety of higher dulaglutide doses (3.0 mg and 4.5 mg) when added to metformin in patients with type 2 diabetes: a phase 3, randomized, double-blind, parallel arm study (AWARD-11). J Endocr Soc. 2020;4(suppl 1):A1036. Endocrine Society abstract OR26-08. https://doi.org/10.1210/jendso/bvaa046.2057

6Data on file, Eli Lilly and Company and/or one of its subsidiaries.

Datum fӧr senaste ӧversyn October 05, 2020


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