|Year : 2022 | Volume
| Issue : 3 | Page : 314-316
Serious adverse effects following use of liraglutide in individuals with type 2 diabetes
Benjamin M Easow, Milly Mathew, Urjitha Rajagopalan, P Nagarajan, Georgi Abraham
MGM Healthcare, No. 72 Nelson Manickam Road, Chennai 600029, Tamil Nadu, India
|Date of Submission||22-Jul-2022|
|Date of Decision||05-Aug-2022|
|Date of Acceptance||05-Aug-2022|
|Date of Web Publication||29-Aug-2022|
Prof. Georgi Abraham
Department of Nephrology, MGM Healthcare, No. 72 Nelson Manickam Road, Chennai 600029, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Glucagon-like peptide-1 (GLP-1) analog liraglutide is extensively used for type 2 diabetes mellitus, especially in those with overweight and cardiovascular risk factors. The risk benefit ratio favors their use. The life-threatening complications such as cholecystitis and pancreatitis are infrequently reported. Here we report two patients who developed recurrent gallstone diseases with cholestatic jaundice and acute pancreatitis in a male patient and an asymptomatic large gallstone stone in a female kidney transplant patient with no previous evidence of gallstone disease. This highlights the importance of surveillance screening in patients on liraglutide to prevent the development of complications.
Keywords: Acute pancreatitis, complications of liraglutide, gallstone diseases, need for surveillance, type 2 diabetes mellitus
|How to cite this article:|
Easow BM, Mathew M, Rajagopalan U, Nagarajan P, Abraham G. Serious adverse effects following use of liraglutide in individuals with type 2 diabetes. J Diabetol 2022;13:314-6
| Background|| |
India with the second largest population in the world has a burden of diabetes with an overall prevalence of 7.3%, with a percentage higher in urban areas (11.2%) than in rural areas (5.2%). Being a developing country with socio-economic issues, blood sugar management is a challenging problem with only less than 25% of the people with diabetes achieve optimal blood sugar levels. The cost of insulin analogs and new injectable drugs are a burden to majority of the patients. While implementing newer therapies, the surveillance for adverse effects are non-existent in geographical areas of the country with poor healthcare infrastructure.
The GLP-1 analogs such as liraglutide and dulaglutide are useful in diabetic control by reducing appetite, promoting weight loss, glucagon suppression, and delaying gastric emptying. However, there are adverse effects which are life-threatening.
Here we describe two patients with recurrent gall stones and pancreatitis while using liraglutide.
| Cases|| |
A type 2 diabetes mellitus (T2DM) male, 69 years old, with a history of hypertension and diabetes for 23 years with an HbA1c between 6.5 and 7.1, was on liraglutide 1.2 U for 3 years along with metformin 500 mg twice a day and glimepiride 1 mg twice a day. The lipid profile was within normal limits. Serum creatinine was 1 mg/dL and body mass index was 26 kg/m2. The patient developed severe right hypochondrial pain following fatty meals on October 29, 2019 with loss of appetite and nausea. There was yellowish discoloration of his urine, which was progressive. Ultrasound abdomen showed a 7 mm size stone in the distal part of the common bile duct 2 cm proximal to the ampulla of Vater [Figure 1](a).
|Figure 1: (a) Stone at common bile duct in 2019. (b) 8 mm stone at ampulla of Vater in 2021|
Click here to view
A diagnosis of cholelithiasis with obstructive jaundice was made, and endoscopic retrograde cholangiopancreatography (ERCP) was done along with stone crushing, removal, and a stent was placed 3 days later with relief of abdominal pain and decline in bilirubin. The patient continued the same dosage of liraglutide with a surveillance ultrasonography every month to identify the formation of new gallstones.
On September 20, 2021, the patient had sudden onset of vomiting followed by abdominal pain in the epigastric region with loss of appetite. Relevant blood examination revealed serum amylase and lipase levels of 6500 and 7200 IU, respectively. Magnetic resonance imaging (MRI) scan revealed a stone of 8 mm in the ampulla of Vater producing dilation of the pancreatic duct. An ERCP was done but could not localize a stone and the attempt was given up. Liraglutide was discontinued and was switched over to ryzodec without changing the other hypoglycemic agents. The pancreatic enzymes came down to 150 and 100, respectively, and after 2 weeks a repeat MRI showed the absence of stone in the ampulla of Vater [Figure 1(a) and (b)].
A 47-year-old lady with a functioning kidney transplant (2007) from her father developed weight gain and new-onset diabetes mellitus 2 years ago. She was treated with metformin, and liraglutide of 1.2 U S/C per day was added a year ago. During follow-up, in the transplant clinic, a 6-month ultrasound examination of the abdomen was normal. She had a slight reduction in weight, but a surveillance ultrasound of the abdomen showed a large gallstone in the gallbladder which was asymptomatic. She had no lithogenic bile and no history of past cholelithiasis. Her investigations showed raised alkaline phosphatase: 164.2 IU/L and WBC: 13,400/µL with all other investigations within the reference range. She underwent a laparoscopic cholecystectomy on 25/09/2021 after discontinuing liraglutide [Figure 2].
The patient remains asymptomatic and her current medications are tacrolimus 0.05 mg PO BID, sodium salt of mycophenolic acid 360 mg PO HS, prednisolone 5 mg/2.5 mg alternate days, oral hypoglycemic drugs, and inj. ryzodec 10 U before breakfast.
| Discussion|| |
Gastrointestinal (GI) events such as nausea, vomiting, diarrhea, dyspepsia, and constipation were the commonly reported adverse events in Indian studies with liraglutide and the Liraglutide Effect and Action in Diabetes (LEAD) program. The GI events were often dose-dependent and mild in nature and diminished gradually on the continuation of therapy over 4–6 weeks or more. In other randomized controlled trial studies such as the LEADER trial, there was an increased risk of acute gallbladder or biliary disease with liraglutide vs. placebo (n = 141 of 4668 vs. n = 88 of 4672 patients, respectively; hazard ratio 1.60; 95% confidence interval 1.23, 2.09; P < 0.001). More patients treated with liraglutide had uncomplicated gallbladder stones (n = 16 and n = 5 for liraglutide and placebo, respectively), complicated gallbladder stones (n = 52 and n = 40), cholecystitis (n = 51 and n = 33), and biliary obstruction (n = 25 and n = 16). These results were found to be consistent with findings from a trial of liraglutide 3.0 mg conducted in people without T2DM, in which more gallbladder-related events were observed in liraglutide-treated participants compared with placebo-treated participants., Gallbladder events are said to be the most common cause of acute pancreatitis, accounting for above 45% of the cases., While the numbers of relevant events were low, the LEADER trial demonstrated that fewer patients treated with liraglutide experienced acute pancreatitis compared with those treated with placebo (n = 18 and n = 23 for liraglutide and placebo, respectively). These side effects have to be recognized early. This opens an avenue to interact with patients who are on GLP-1 analogs such as liraglutide to look at the prevalence of these adverse effects.
| Conclusion|| |
Since the incidence of obesity and diabetes is high in India, combination medications with GLP-1 agonists such as liraglutide are widely used. The possibility of these medications causing recurrent gallstones and pancreatitis should be kept in mind. Clinicians should closely monitor the patients for these complications.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Anjana RM, Deepa M, Pradeepa R, Mahanta J, Narain K, Das HK, et al
; ICMR–INDIAB Collaborative Study Group. Prevalence of diabetes and prediabetes in 15 states of India: Results from the ICMR-INDIAB population-based cross-sectional study. Lancet Diabetes Endocrinol 2017;5:585-96.
Anirban M, Soumyabrata RC, Debmalya S, Bhattacharjee K Liraglutide—Indian experience. Indian J Endocrinol Metab 2018;22:818-26.
Nauck MA, Muus Ghorbani ML, Kreiner E, Saevereid HA, Buse JB; LEADER Publication Committee on Behalf of the LEADER Trial Investigators. Effects of liraglutide compared with placebo on events of acute gallbladder or biliary disease in patients with type 2 diabetes at high risk for cardiovascular events in the LEADER randomized trial. Diabetes Care 2019;42:1912-20.
Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, et al
; SCALE Obesity and Prediabetes NN8022-1839 Study Group. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med 2015;373:11-22.
[Figure 1], [Figure 2]