Prevalence and causes
Millions of Americans are at risk of life-threatening complications due to severe hypertriglyceridemia (sHTG)1,4
Defining sHTG
sHTG
severe hypertriglyceridemia
sHTG is defined by fasting triglyceride levels 500 mg/dL and above, and characterized by an increased risk of acute pancreatitis (AP), atherosclerotic cardiovascular disease (ASCVD), and other associated morbidities1,5-7


More than 3 million American adults are estimated to have sHTG, although the true prevalence may be even higher4
Current guidelines recommend diagnosing sHTG based on fasting serum triglyceride levels. However, people are in a postprandial state for most of the day. Therefore, a patient's true risk of sHTG and related complications may be greater than what fasting levels may indicate.3,8
sHTG can be caused by a combination of several factors1,9,10
Lifestyle (eg, high alcohol intake, poor diet)
Medications (eg, antidepressants, oral contraceptives, antiretrovirals)
Clinical conditions (eg, diabetes, obesity, HIV, pregnancy)
Genetic factors (eg, familial chylomicronemia syndrome, multifactorial chylomicronemia syndrome)
sHTG and its dangers are underappreciated and require urgent action.1,3,5,8,11
Current approach
Existing treatment approaches for addressing severe hypertriglyceridemia (sHTG) are insufficient11-14
Limitations of current approaches
Lifestyle changes
Lifestyle modifications such as diet and exercise have proven to be an unreliable means of lowering triglycerides, as they depend on patient adherence.12
Therapies
Omega-3 fatty acids
American Association of Clinical Endocrinology (AACE) clinical practice guidelines 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.11
Fibrates and statins
Fibrates and statins are some of the most commonly used lipid-lowering therapies; however, they do not reduce triglyceride (TG) levels sufficiently in all patients with sHTG. According to the American Heart Association (AHA), fibrates lower TG levels by approximately 30%-50%, and statins lower TG levels by approximately 10%-30%.13
Niacin
The AACE clinical practice guideline on pharmacologic management for dyslipidemia does not recommend niacin in adults with sHTG (≥500 mg/dL) due to significant adverse effects.11
GLP-1
Though some patients with sHTG may be receiving treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist for diabetes or weight loss, it's important to note that GLP-1s have been found to increase the risk of gastrointestinal adverse events, including acute pancreatitis.14
Lifestyle modifications and currently available pharmacologic therapies are limited in their ability to sufficiently lower triglyceride levels in patients with sHTG, resulting in continued risk for acute pancreatitis and atherosclerotic cardiovascular disease.1,11-16
Postprandial spikes
Severe hypertriglyceridemia (sHTG) is volatile due to postprandial spikes in triglyceride levels17,18
The risks associated with sHTG are underestimated and life-threatening, as triglycerides—unlike other lipids—can fluctuate greatly between fasting and nonfasting states3,5
The additive effect of multiple meals can cause a substantial
postprandial TG peak, with levels elevated for most of
the day.8
As triglycerides surpass 880 mg/dL, chylomicrons become the predominant triglyceride-rich lipoprotein (TRL), resulting in increased risk of acute pancreatitis (AP) and continued atherosclerotic cardiovascular disease (ASCVD) risk.17,19
The primary risks when triglyceride levels reach 500 mg/dL and above are AP and ASCVD, due to the predominance of TRLs such as chylomicrons and very-low-density lipoproteins (VLDL).1
Due to the postprandial increases of triglycerides and the risk associated with escalating levels, it is critical to treat sHTG aggressively and appropriately.1,17,18
A patient's risk for serious health complications varies depending on their triglyceride levels and medical history1
Choose a patient journey to explore

She experienced her first AP attack. Will there be another?

His diabetes and triglycerides were out of control.

His cardiologist suspected there was more to his sHTG.

When the standard of care isn't working, it's time to dig deeper.
Not real patients; actor portrayals and generated models.

Sandra, 49
Has severe hypertriglyceridemia (sHTG) with a history of acute pancreatitis (AP)
- Sandra was diagnosed with sHTG at age 47, when multiple lipid panels revealed elevated triglyceride (TG) levels of 864 mg/dL and 873 mg/dL (fasting)
- Sandra was prescribed a fibrate, which she stopped taking shortly afterward due to myalgias
- Sandra experienced her first episode of AP at age 48. She was prescribed an EPA and a statin, to which she adhered, but her TGs remained above 500 mg/dL
- Sandra has implemented lifestyle changes but is still feeling anxious that she might experience another AP episode if she doesn't get her TG levels under control
- Sandra was diagnosed with sHTG at age 47, when multiple lipid panels revealed elevated triglyceride (TG) levels of 864 mg/dL and 873 mg/dL (fasting)
- Sandra was prescribed a fibrate, which she stopped taking shortly afterward due to myalgias
- Sandra experienced her first episode of AP at age 48. She was prescribed an EPA and a statin, to which she adhered, but her TGs remained above 500 mg/dL
- Sandra has implemented lifestyle changes but is still feeling anxious that she might experience another AP episode if she doesn't get her TG levels under control

Lawrence, 62
Has severe hypertriglyceridemia (sHTG) and type 2 diabetes mellitus (T2DM)
- Lawrence's endocrinologist started him on metformin and a statin and recommended lifestyle modification
- With the medications and lifestyle changes, his A1c improved and was at goal; however, his elevated triglycerides (TGs) persisted in the range of 789 mg/dL to 873 mg/dL (fasting)
- An EPA, and eventually a fibrate, were prescribed to control Lawrence's TG levels. Both were ineffective in lowering his TG levels below 500 mg/dL
- The endocrinologist had considered treating him with a GLP-1 receptor agonist to help with weight loss but was hesitant due to the increased risk of pancreatitis
- Lawrence is worried his endocrinologist won't find a treatment to lower his TGs, leaving him at risk for serious health complications
- Lawrence's endocrinologist started him on metformin and a statin and recommended lifestyle modification
- With the medications and lifestyle changes, his A1c improved and was at goal; however, his elevated triglycerides (TGs) persisted in the range of 789 mg/dL to 873 mg/dL (fasting)
- An EPA, and eventually a fibrate, were prescribed to control Lawrence's TG levels. Both were ineffective in lowering his TG levels below 500 mg/dL
- The endocrinologist had considered treating him with a GLP-1 receptor agonist to help with weight loss but was hesitant due to the increased risk of pancreatitis
- Lawrence is worried his endocrinologist won't find a treatment to lower his TGs, leaving him at risk for serious health complications

Michael, 58
Has severe hypertriglyceridemia (sHTG), hypertension, and coronary artery disease (CAD) and was diagnosed with multifactorial chylomicronemia syndrome
- Michael was following up with his cardiologist when a repeat lipid panel showed an elevated triglyceride (TG) level of 1512 mg/dL (fasting)
- Michael was on a statin for his sHTG and CAD. The statin lowered his TG levels by 10%. Concurrent medications included an ACE inhibitor for hypertension, which was well controlled
- After seeing suboptimal results in TG lowering with a statin, Michael's cardiologist added a fibrate, and eventually an EPA, to his treatment plan, all of which were ineffective in lowering his TGs below 880 mg/dL
- Michael's cardiologist suspected a genetic cause and used the NAFCS scoring tool to rule out FCS, a monogenic genetic form of sHTG. Michael was finally diagnosed with MCS, a polygenic form of sHTG, commonly seen with comorbid conditions22,23
- Michael was following up with his cardiologist when a repeat lipid panel showed an elevated triglyceride (TG) level of 1512 mg/dL (fasting)
- Michael was on a statin for his sHTG and CAD. The statin lowered his TG levels by 10%. Concurrent medications included an ACE inhibitor for hypertension, which was well controlled
- After seeing suboptimal results in TG lowering with a statin, Michael's cardiologist added a fibrate, and eventually an EPA, to his treatment plan, all of which were ineffective in lowering his TGs below 880 mg/dL
- Michael's cardiologist suspected a genetic cause and used the NAFCS scoring tool to rule out FCS, a monogenic genetic form of sHTG. Michael was finally diagnosed with MCS, a polygenic form of sHTG, commonly seen with comorbid conditions22,23

Maria, 53
Has severe hypertriglyceridemia (sHTG)
- Maria had a lipid panel as part of her routine physical exam with her primary care doctor. It showed an elevated triglyceride (TG) level of 863 mg/dL (fasting). Repeat lipid panels showed consistent results
- After seeing that Maria's TGs were above 500 mg/dL, her doctor prescribed an EPA and lifestyle modifications. The EPA only slightly reduced her TG level, which remained above 500 mg/dL
- Her doctor then prescribed a statin, and eventually a fibrate, both of which failed to lower her TG levels below 500 mg/dL
- Maria had a lipid panel as part of her routine physical exam with her primary care doctor. It showed an elevated triglyceride (TG) level of 863 mg/dL (fasting). Repeat lipid panels showed consistent results
- After seeing that Maria's TGs were above 500 mg/dL, her doctor prescribed an EPA and lifestyle modifications. The EPA only slightly reduced her TG level, which remained above 500 mg/dL
- Her doctor then prescribed a statin, and eventually a fibrate, both of which failed to lower her TG levels below 500 mg/dL
A1c=glycated hemoglobin; ACE inhibitor=angiotensin-converting enzyme inhibitor; AP=acute pancreatitis; ASCVD=atherosclerotic cardiovascular disease; BMI=body mass index; CVD=cardiovascular disease; EPA=eicosapentaenoic acid; FCS=familial chylomicronemia syndrome; GLP-1 receptor agonist=glucagon-like peptide-1 (GLP-1) agonist; MCS=multifactorial chylomicronemia syndrome; NAFCS scoring tool=North American Familial Chylomicronemia Syndrome scoring tool.
References
- 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.
- 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.
- 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.
- Data on file. sHTG prevalence. Ionis Pharmaceuticals; 2024.
- Gurevitz C, Chen L, Muntner P, Rosenson RS. Hypertriglyceridemia and multiorgan disease among U.S. adults. JACC Adv. 2024;3(5):100932.
- Kessler AS, Aggio D, Howard EM, et al. A qualitative study to explore the patient experience of hypertriglyceridemia-related acute pancreatitis. J Clin Lipidol. Published online April 10, 2025.
- Kessler AS, Zhang C, McStocker S, et al. Study-start characteristics of individuals with severe hypertriglyceridemia (sHTG) in an app-based home-reported outcomes study evaluating disease burden and treatment patterns. Abstract accepted for presentation at: PancreasFest; July 24-25, 2025; Pittsburgh, PA.
- Keirns BH, Sciarrillo CM, Koemel NA, Emerson SR. Fasting, non-fasting and postprandial triglycerides for screening cardiometabolic risk. J Nutr Sci. 2021;10:e75.
- 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.
- 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.
- 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.
- Santos-Baez LS, Ginsberg HN. Hypertriglyceridemia—causes, significance, and approaches to therapy. Front Endocrinol (Lausanne). 2020;11:616.
- 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.
- Aldhaleei WA, Abegaz TM, Bhagavathula AS. Glucagon-like peptide-1 receptor agonists associated gastrointestinal adverse events: a cross-sectional analysis of the National Institutes of Health All of Us Cohort. Pharmaceuticals (Basel). 2024;17(2):199.
- Fung MA, Frohlich JJ. Common problems in the management of hypertriglyceridemia. CMAJ. 2002;167(11):1261-1266.
- Shemesh E, Zafrir B. Hypertriglyceridemia-related pancreatitis in patients with type 2 diabetes: links and risks. Diabetes Metab Syndr Obes. 2019;12:2041-2052.
- 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.
- D'Erasmo L, Di Costanzo A, Cassandra F, et al. Spectrum of mutations and long-term clinical outcomes in genetic chylomicronemia syndromes. Arterioscler Thromb Vasc Biol. 2019;39(12):2531-2541.
- Yuan G, Al-Shali KZ, Hegele RA. Hypertriglyceridemia: its etiology, effects and treatment. CMAJ. 2007;176(8):1113-1120.
- Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Circulation. 2019;139(25):e1046-e1081.
- Sanchez RJ, Ge W, Wei W, Ponda MP, Rosenson RS. The association of triglyceride levels with the incidence of initial and recurrent acute pancreatitis. Lipids Health Dis. 2021;20(1):72.
- Pallazola VA, Sajja A, Derenbecker R, et al. Prevalence of familial chylomicronemia syndrome in a quaternary care center. Eur J Prev Cardiol. 2020;27(19):2276-2278.
- Paquette M, Bernard S. The evolving story of multifactorial chylomicronemia syndrome. Front Cardiovasc Med. 2022;9:886266.