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June Blog Post: T2DM Management complicated by gastroparesis

By Katelyn O'Brien posted 16 days ago

  

T2DM management complicated by gastroparesis

Prepared by: Courtney Cameron, PharmD, PGY2 Ambulatory Care Pharmacy Resident, Boston Medical Center. Reviewed by: Katelyn O'Brien, PharmD, BCPS, CDCES Clinical Pharmacy Specialist, Boston Medical Center.

What is diabetic gastroparesis?

Gastroparesis is an autonomic neuropathic complication that more commonly affects individuals with T1DM or longstanding T2DM and may occur as a result of damaged nerves within the enteric nervous system.1,2  It is estimated that 20-50%3 of individuals with diabetes are affected by gastroparesis, while 30% of individuals with gastroparesis have comorbid diabetes4. Gastroparesis is important to recognize in patients with diabetes because the condition increases the risk for dysglycemia, malnutrition, hospitalization, development of bezoars, and poor quality of life.1,2

Gastroparesis is a chronic, relapsing condition characterized by delayed gastric emptying in the absence of other explainable causes (such as mechanical obstruction).1,2 Risk factors include having a diagnosis of T1DM, being over the age of 40 or a woman, and having a 10+ year history of diabetes. Additionally, symptoms typically vary person-to-person though vomiting is a known hallmark symptom. Other symptoms may include postprandial fullness, early satiety and nausea especially after meals, bloating, and upper abdominal pain. Diagnosis should be confirmed by the gold standard, scintigraphy.

Gastroparesis in the setting of diabetes makes blood sugar control imperative because blood glucose directly effects stomach functions, and vice versa1,2. Gastroparesis can especially make the management of diabetes complex because gastroparesis causes unpredictable though delayed food absorption, that in turn, results in erratic blood sugar.

 How is best to manage diabetes in the setting of gastroparesis?

                Principally, the best management of diabetes complicated by gastroparesis is to discontinue offending agents, such as GLP-1s or metformin.2,5 As we know, GLP-1 agents cause abdominal pain, constipation, diarrhea, nausea, vomiting, decreased appetite, and dyspepsia that can worsen symptoms of gastroparesis [Table 1].6 The mechanism that contributes to these side effects is dose related and possibly related to delayed gastric emptying. Metformin is also associated with reversible gastrointestinal side effects that include diarrhea, nausea, flatulence, dyspepsia, vomiting, and abdominal pain.9 The incidence of side effects is generally less with extended release formulations of metformin. The incidence of diarrhea varies from 10% with the extended release formulation as opposed to 53% with the immediate release formulation. The incidence of nausea and vomiting varies from 7% with the extended release formulation as opposed to 26% with the immediate release formulation. Interestingly, DPP-4 inhibitors such as linagliptin or sitagliptin are not associated with delayed gastric emptying and can be considered along with other standard of care agents including SGLT2 inhibitors or insulin in T2DM.3,5 Due to comorbidities such as CKD, insulin may inadvertently become the preferred agent of choice in patients with gastroparesis and T2DM. Insulin remains the mainstay of therapy for T1DM patients with gastroparesis.

                Optimal management of patients with diabetes associated with gastroparesis will also include the use of continuous glucose monitors (CGMs).11 CGMs provide robust data on blood sugar control, and therefore may contribute to improved glucose control, especially for patients with variable glucose, as seen in gastroparesis. No studies to date have specifically evaluated the use of CGM in patients with gastroparesis-associated diabetes.

 

Table 1: Incidence of GI effects for common GLP1s6-8

Abdominal Pain

Nausea

Vomiting

Rybelsus (oral semaglutide)

6-10%

11-20%

6-8%

Ozempic (subcutaneous semaglutide)

16-44%

5-24%

Trulicity (dulaglutide)

7-9%

12-21%

6-15%

Victoza (liraglutide)

5%

39-42%

16%

 

 

What insulins should be chosen in the management of patients with gastroparesis?

                Delayed gastric emptying, as is characteristic for all patients with gastroparesis, complicates the use of insulin and optimal diabetes management for many patients.10 To provide an example, typically rapid-acting insulin is administered 15 minutes before eating so that insulin will begin to be effective as the stomach empties and glucose is absorbed. However, the timing of rapid-acting insulin in a patient with gastroparesis is not so clear, due to the delayed nutrient absorption and change in eating habits around early satiety. A patient may not eat as much food as intended (especially in the case of carb-counting), or they may vomit their meal before the stomach empties. Both of these situations can result in insulin effect before or without adequate glucose in the blood stream, leading to hypoglycemia and potential danger.

                The optimal mealtime insulin regimen may consider both delayed absorption of glucose after meals and the potential for a smaller meal eaten than intended by the patient. Strategies could include dosing rapid-acting insulins 30-minutes after the start of eating (instead of the typical 15 minutes before meals), or split-bolus dosing, whereby a patient takes 50% of their rapid acting insulin before a meal, and 50% 30-minutes after the start of a meal.11 Alternatively, one could consider swapping rapid acting insulin for regular insulin due to the difference in pharmacokinetics that may be a benefit in the setting of delayed gastric emptying [see figure below].

 

 

Summary

                In summary, T2DM complicated by gastroparesis is a fairly common comorbidity, especially in patients with long-standing diabetes, that necessitates a careful consideration of appropriate therapy. Patients with gastroparesis may experience nausea and vomiting, especially after meals, as well as early satiety and abdominal pain that is made worse by offending agents such as GLP-1s and metformin. Due to comorbidities such as CKD, insulin may often be the agent of choice for blood sugar management. However, patients with gastroparesis often have erratic blood sugars due to delayed gastric emptying. Therefore, these patients may be optimally managed with the help of CGMs and careful consideration of mealtime insulin pharmacokinetics.

              

References:

  1. Petri M, Singh I, Baker C, Underkofler C, Rasouli N. Diabetic gastroparesis: An overview of pathogenesis, clinical presentation and novel therapies, with a focus on ghrelin receptor agonists. J Diabetes Complications. 2021;35(2):107733. doi:10.1016/j.jdiacomp.2020.107733
  2. A Review of Diabetic Gastroparesis for the Community Pharmacist. USPharmacist. Available at: https://www.uspharmacist.com/article/a-review-of-diabetic-gastroparesis-for-the-community-pharmacist. Accessed 22 March 2022.
  3. Krishnasamy S, Abell TL. Diabetic Gastroparesis: Principles and Current Trends in Management. Diabetes Ther. 2018;9(Suppl 1):1-42. doi:10.1007/s13300-018-0454-9
  4. Ye Y, Yin Y, Huh SY, et al. Epidemiology, Etiology, and Treatment of Gastroparesis: Real-World Evidence From a Large US National Claims Database. Gastroenterology. 2022;162(1):109-121.e5. doi:10.1053/j.gastro.2021.09.064
  5. American Diabetes Association Professional Practice Committee; American Diabetes Association Professional Practice Committee:, Draznin B, et al. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022;45(Supplement_1):S125-S143. doi:10.2337/dc22-S009
  6. In: Lexi-drugs online [Internet Database]. Hudson (OH): Lexicomp, Inc.; 2016 [Accessed 24 March 2022].
  7. In: Lexi-drugs online [Internet Database]. Hudson (OH): Lexicomp, Inc.; 2016 [Accessed 24 March 2022].
  8. In: Lexi-drugs online [Internet Database]. Hudson (OH): Lexicomp, Inc.; 2016 [Accessed 24 March 2022].
  9. In: Lexi-drugs online [Internet Database]. Hudson (OH): Lexicomp, Inc.; 2016 [Accessed 24 March 2022].
  10. How Does Gastroparesis Affect People with Diabetes? NIDDK. Available at: https://www.niddk.nih.gov/health-information/professionals/diabetes-discoveries-practice/how-gastroparesis-affect-people-with-diabetes. Accessed 24 March 2022.
  11. Krishnasamy S, Abell TL. Diabetic Gastroparesis: Principles and Current Trends in Management. Diabetes Ther. 2018;9(Suppl 1):1-42. doi:10.1007/s13300-018-0454-9.
  12. https://www.usmed.com/blog/diabetes/diabetes-gastroparesis-symptoms-causes-treatment/
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