Unmet need of severe hypertriglyceridemia (sHTG)

sHTG demands urgent action to reduce potentially life-threatening risks such as acute pancreatitis and atherosclerotic cardiovascular disease. However, underestimation of sHTG and limitations of current treatments continue to pose challenges for effective management.1-8

Jump to:

About sHTG

Severe hypertriglyceridemia (sHTG) is defined as fasting triglyceride levels ≥500 mg/dL1

At fasting triglyceride levels ≥500 mg/dL, the risks of acute pancreatitis (AP) and atherosclerotic cardiovascular disease (ASCVD) rise and require immediate attention.1-3

Image with text: At fasting triglyceride levels ≥500 mg/dL, the risks of acute pancreatitis (AP) and atherosclerotic cardiovascular disease (ASCVD) rise and require immediate attention.

Causes

Severe hypertriglyceridemia (sHTG) is typically caused by a combination of several factors1,13,14

Lifestyle factors, medications, clinical conditions, and underlying genetic factors can elevate triglyceride levels.1,13,14

Image with text: Lifestyle factors, medications, clinical conditions, and underlying genetic factors can elevate triglyceride levels.

HIV=human immunodeficiency.

Prevalence and postprandial spikes

The true prevalence of severe hypertriglyceridemia (sHTG) is likely higher than current estimates4-7

Image of the United States with text overlay saying "More than 3 million American adults" referencing a statistic of how many Americans live with sHTG

Millions of Americans live with sHTG15

However, the true prevalence of sHTG is likely higher than current estimates due to several factors4–7

Guidelines call for testing of fasting triglyceride levels

  • Patients are in a postprandial state most of the day, allowing severe elevations to be missed5,7,16

Lack of ICD-10 code for sHTG

  • Classification under broader hyperlipidemia terms limits understanding of true sHTG prevalence4

Signs and symptoms may not be recognized

  • Elevated triglycerides as a cause of acute abdominal pain and acute pancreatitis is often overlooked17

ICD-10=International Classification of Diseases, 10th Revision.

Triglycerides are dynamic and can surge dramatically after meals5,16

Fasting triglyceride levels provide an important baseline, but postprandial triglyceride excursions can be substantial. Following a typical meal, dietary triglycerides peak over 3 to 5 hours. Because people typically eat multiple times per day, triglyceride levels accumulate and keep them in a postprandial state for most of the day.5

Estimated triglyceride kinetics for average US male with normal
triglycerides (122 mg/dL) following the typical Western dietary pattern5*

Line chart showing the estimated triglyceride kinetics for the average US male with normal triglycerides (122 mg/dL)

For people with sHTG, how high can triglycerides rise over a typical day of eating?

*

Estimate based on average US male who consumes approximately 2400 kcal/day, 35% of which are from fat, over 4 to 5 meals and snacks. These averages equate to consumption of approximately 93 g of fat each day, approximately 23 g per meal if divided across 4 meals. Figure adapted from Keirns BH, et al. J Nutr Sci. 2021.5

†

Normal triglyceride levels were defined as <150 mg/dL.3

Existing treatment approaches

Available treatment approaches rarely meet the challenge of severe hypertriglyceridemia (sHTG)

Current standard of care for sHTG

Lifestyle changes

Lifestyle modifications such as diet and exercise are ineffective at lowering triglycerides if patient adherence is low.18

Therapies

Fibrates

Fibrates are some of the most commonly used lipid-lowering therapies; however, they do not reduce triglyceride levels sufficiently in all patients with sHTG.8

Omega-3 fatty acids

An American Association of Clinical Endocrinology clinical practice guideline on pharmacologic management of adults with dyslipidemia found insufficient evidence that EPA/EPA+DHA (omega-3 fatty acids) prevent pancreatitis, the main complication associated with sHTG.1,19

Statins

Statins are another common lipid-lowering therapy that does not reduce triglyceride levels sufficiently in all patients with sHTG.8

Other considerations

GLP-1 receptor agonists

GLP-1 receptor agonists can significantly improve weight loss and glycemic control; however, their impact on triglyceride reduction is modest and often insufficient for patients with sHTG.20

DHA=docosahexaenoic acid; EPA=eicosapentaenoic acid; GLP-1=glucagon-like peptide-1.

References

References

  1. Virani SS, Morris PB, Agarwala A, et al. 2021 ACC expert consensus decision pathway on the management of ASCVD risk reduction in patients with persistent hypertriglyceridemia: a report of the American College of Cardiology solution set oversight committee. J Am Coll Cardiol. 2021;78(9):960-993.

  2. Nawaz H, Koutroumpakis E, Easler J, et al. Elevated serum triglycerides are independently associated with persistent organ failure in acute pancreatitis. Am J Gastroenterol. 2015;110(10):1497-1503.

  3. Arca M, Veronesi C, D’Erasmo L, et al. Association of hypertriglyceridemia with all-cause mortality and atherosclerotic cardiovascular events in a low-risk Italian population: the TG-REAL retrospective cohort analysis. J Am Heart Assoc. 2020;9(19):e015801.

  4. Laforge R. Commonly used lipidcentric ICD-10 (ICD-9) codes. National Lipid Association. November 2015. Accessed December 3, 2025. https://www.lipid.org/sites/default/files/files/ICD-10_rev_Dec_10.pdf

  5. Keirns BH, Sciarrillo CM, Koemel NA, Emerson SR. Fasting, non-fasting and postprandial triglycerides for screening cardiometabolic risk. J Nutr Sci. 2021;10:e75.

  6. Baass A, Paquette M, Lam O, Hofer K, Collet J, McClain MR. Prevalence, incidence, and definition of severe hypertriglyceridemia: a comprehensive review and weighted summary. J Clin Lipidol. 2025;19(6):1550-1563.

  7. Goldberg RB, Chait A. A comprehensive update on the chylomicronemia syndrome. Front Endocrinol (Lausanne). 2020;11:593931.

  8. Skulas-Ray AC, Wilson PWF, Harris WS, et al. Omega-3 fatty acids for the management of hypertriglyceridemia: a science advisory from the American Heart Association. Circulation. 2019;140(12):e673-e691.

  9. Ginsberg HN, Packard CJ, Chapman MJ, et al. Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies—a consensus statement from the European Atherosclerosis Society. Eur Heart J. 2021;42(47):4791-4806.

  10. Kessler AS, Baum SJ, Kutrieb E, et al. Healthcare utilization and expenditures among adults with severe hypertriglyceridemia in US clinical practice. Poster presented at: National Lipid Association Annual Scientific Sessions; May 29-June 1, 2025; Miami, FL.

  11. Yuan G, Al-Shali KZ, Hegele RA. Hypertriglyceridemia: its etiology, effects and treatment. CMAJ. 2007;176(8):1113-1120.

  12. Rashid N, Sharma PP, Scott RD, Lin KJ, Toth PP. Severe hypertriglyceridemia and factors associated with acute pancreatitis in an integrated health care system. J Clin Lipidol. 2016;10(4):880-890.

  13. Hegele RA, Ahmad Z, Ashraf A, et al. Development and validation of clinical criteria to identify familial chylomicronemia syndrome (FCS) in North America. J Clin Lipidol. 2025;19(1)(online-only supplementary material):83-94.

  14. Hegele RA, Ahmad Z, Ashraf A, et al. Development and validation of clinical criteria to identify familial chylomicronemia syndrome (FCS) in North America. J Clin Lipidol. 2025;19(1):83-94.

  15. Christian JB, Bourgeois N, Snipes R, Lowe KA. Prevalence of severe (500 to 2,000 mg/dl) hypertriglyceridemia in United States adults. Am J Cardiol. 2011;107(6):891-897.

  16. Hegele RA, Ginsberg HN, Chapman MJ, et al. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol. 2014;2(8):655-666. 

  17. Nashtar MA, Kempener J, Gohman U, et al. Hypertriglyceridemia screening in acute pancreatitis: diagnostic blind spot in clinical routine. Dig Dis Sci. Published online September 13, 2025. doi:10.1007/s10620-025-09366-4

  18. Santos-Baez LS, Ginsberg HN. Hypertriglyceridemia—causes, significance, and approaches to therapy. Front Endocrinol (Lausanne). 2020;11:616. 

  19. Patel SB, Wyne KL, Afreen S, et al. American Association of Clinical Endocrinology clinical practice guideline on pharmacologic management of adults with dyslipidemia. Endocr Pract. 2025;31(2):236-262.

  20. Rivera FB, Chin MNC, Pine PLS, et al. Glucagon-like peptide 1 receptor agonists modestly reduced low-density lipoprotein cholesterol and total cholesterol levels independent of weight reduction: a meta-analysis and meta-regression of placebo controlled randomized controlled trials. Curr Med Res Opin. 2025;41(1):185-197.

  21. Kirkpatrick CF, Sikand G, Petersen KS, et al. Nutrition interventions for adults with dyslipidemia: a clinical perspective from the National Lipid Association. J Clin Lipidol. 2023;17(4):428-451.