Acebutolol produced a nonsignificant decrease in HDL cholesterol level. The concentration of apolipoprotein A-I increased slightly during pindolol therapy. Beta blockers, with the exception of pindolol, decrease the concentration of serum free fatty acids.
Beta-adrenergic receptor blockers. Adverse effects and drug interactions. Hypertension ; 11 : II21—9. Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry ; 33 : — Implications of genetic variability of human beta 2-adrenergic receptor structure. Pulm Pharmacol ; 8 : 1— The effect of common polymorphisms of the beta2-adrenergic receptor on agonist-mediated vascular desensitization. N Engl J Med ; : — Strosberg AD.
Structure, function, and regulation of adrenergic receptors. Protein Sci ; 2 : — Targeted gene disruption reveals a leptin-independent role for the mouse beta3-adrenoceptor in the regulation of body composition.
J Clin Invest ; : — Targeted disruption of the beta 3-adrenergic receptor gene. J Biol Chem ; : — Association of the Trp64Arg mutation of the beta3-adrenergic receptor with fatty liver and mild glucose intolerance in Japanese subjects. Clin Chim Acta ; : — Association of a polymorphism in the beta 3-adrenergic-receptor gene with features of the insulin resistance syndrome in Finns.
J Intern Med ; : — An analysis of the link between polymorphisms of the beta2 and beta3 adrenergic receptor gene and metabolic parameters among Polish Caucasians with familial obesity. The Arg Gly beta1-adrenergic receptor gene polymorphism and human fat cell lipolysis.
Guidelines Subcommittee. J Hypertens ; 17 : — The Glu27 allele of the beta2 adrenergic receptor increases the risk of cardiac hypertrophy in hypertension. J Hypertens ; 22 : — Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care ; 26 Suppl 1 : S5—S Rationale for Intervention.
Circulation ; : — Gln27Glu beta2-adrenergic receptor variant is associated with hypertriglyceridemia and the development of fatty liver.
Clin Chim Acta ; : 85— Beta-adrenergic regulation of lipolysis and blood flow in human skeletal muscle in vivo. Am J Physiol ; : E—E Immunological evidence for the presence of hormone-sensitive lipase in rat tissues other than adipose tissue.
Biochem Biophys Res Commun ; : 99— Abraham WT, Iyengar S. Practical considerations for switching beta-blockers in heart failure patients. This review does not address the use of standard lipid-lowering agents in T2DM, since these agents have been discussed in detail in recent guidelines [ 7 , 28 ].
Rather, this review focuses on drugs indicated for the management of hyperglycemia i. Many non-lipid-specific medications widely used in clinical practice have been associated with changes in the lipid profile [ 17 — 19 ]. These changes are summarized in Table 2. Therefore, it should be remembered that, despite significant clinical effects of some medications on the lipid profile, little is known about the clinical relevance of these changes.
However, effects on the lipid profile, whether significant or nominal for any single agent, should not be considered in isolation, since most patients will be taking multiple medications from various classes to treat multiple comorbidities. For this reason, it is important to observe the overall changes governing the ultimate management of dyslipidemia to reduce the ASCVD risk.
An overview of the qualitative effects of the hypoglycemic and antihyperglycemic agents described in the AACE algorithm [ 27 ] on the lipid profile is provided in Table 2.
Current guidelines list metformin, a biguanide, as a first-line oral antihyperglycemic therapy, unless it is contraindicated or not tolerated [ 29 — 31 ]. While its mechanism of action is not well understood, metformin clearly has an inhibitory effect on gluconeogenesis and hepatic glucose output and, contrary to previous opinions, appears not to have any substantial insulin-sensitizing effect in muscle [ 32 ].
Metformin has been associated with small increases in HDL-C levels [ 33 ] that may be more pronounced in Whites and African Americans than in Hispanic populations [ 34 ].
The TG-lowering effect was associated with its glycemic control outcomes. Some reductions in total cholesterol and LDL-C levels were observed independent of glycemic control, but these nominal changes are not considered clinically relevant to ASCVD endpoints.
Thiazolidinediones TZDs , such as pioglitazone and rosiglitazone, stimulate peroxisome proliferator-activated receptors and have differential effects on the basic constituents of the lipid profile. In addition, the increase in LDL-C levels has been shown to be smaller, and the increase in HDL-C greater, with pioglitazone than with rosiglitazone [ 38 ]. Pioglitazone has been shown to decrease LDL-P numbers and to cause more favorable shifts from a predominance of smaller, denser LDL to a larger, more buoyant LDL subtype than rosiglitazone [ 38 ], suggesting an overall reduction in the atherogenic phenotype of the lipid profile [ 41 — 44 ].
TZDs have been associated with favorable changes in inflammatory marker levels i. C-reactive protein and a reduction in visceral fat, but a potentially unfavorable increase in total body weight, partially due to a disproportionate increase in subcutaneous adiposity and fluid retention; the latter carries an increased risk of congestive heart failure in susceptible individuals i.
The single 5. The hypoglycemic agents SUs e. However, a recent meta-analysis of data from placebo-controlled trials found that SUs were associated with significant reductions in total cholesterol and decreases in HDL-C levels [ 37 ]. Since chronic insulin production leads to increases in weight and an increased risk of hypoglycemia, SUs have been discouraged as early-use agents.
However, when used with shorter-acting insulin secretagogues, the glinides repaglinide and nateglinide are favored by the AACE algorithm [ 27 ]. The dose-dependent hypoglycemic risk of SUs makes them unsuitable for patients with hepatic impairments or moderate to severe renal impairments, especially in elderly patients, as their catabolism and clearance involving the liver and kidney, respectively, are reduced [ 23 , 44 ].
Analyses of datasets comparing SUs to metformin, which may itself have cardioprotective properties, have raised concerns regarding the CV safety of this drug class [ 48 ]. Analyses of other datasets did not show a CV safety concern regarding the use of SUs [ 49 ]. The incretin hormones, glucagon-like peptide-1 GLP-1 and glucose-dependent insulinotropic peptide, stimulate insulin secretion in a glucose-dependent fashion.
Patients with T2DM have incretin resistance that can be overcome by enhancing incretin levels [ 50 ]. Dipeptidyl peptidase-4 DPP-4 inhibitors, such as sitagliptin, saxagliptin, linagliptin, alogliptin, and vildagliptin, nominally enhance endogenous incretin levels, which results in a moderate reduction 0. DPP-4 inhibitors are considered weight neutral with modest effects on lipid parameters, including reduction in total cholesterol and TG levels [ 37 ].
Sitagliptin has been found to have modest effects on serum lipid levels in general populations of patients with T2DM and to reduce total cholesterol and LDL-C levels in patients with elevated baseline TG levels [ 23 , 51 , 52 ]. Vildagliptin has been shown to decrease total cholesterol and TG levels to a greater extent than sitagliptin [ 51 ].
In a 1-year retrospective observational study of alogliptin in Japanese patients with T2DM, total cholesterol and LDL-C levels decreased significantly from baseline to 12 months.
In studies in normoglycemic subjects, vildagliptin and alogliptin have been shown to decrease postprandial TG, apo B, and remnant lipoprotein cholesterol levels [ 54 , 55 ]. Similarly, short-term 4 or 6 weeks treatment with vildagliptin and sitagliptin has been shown to reduce postprandial TG and apo B levels, possibly by increasing incretin hormone levels and reducing levels of circulating free fatty acids [ 56 , 57 ].
Furthermore, in a randomized controlled trial in patients with T2DM, Derosa and colleagues observed that, compared with the SU glimepiride, vildagliptin was associated with significantly lower total cholesterol, LDL-C, and TG levels following an oral fat load test [ 58 ]. GLP-1 receptor agonists RAs are analogs of the naturally occurring incretin GLP-1 that have a prolonged half-life and, therefore, prolonged action.
At pharmacologic doses, GLP-1 RAs increase glucose-dependent insulin secretion, decrease glucose-dependent glucagon secretion, and slow gastric emptying, thereby reducing A1C by 0. GLP-1 RAs are understood to have minor beneficial effects on CVD risk, which may be related to their effects to promote weight loss and blood pressure reduction [ 63 , 64 ]. In an analysis of pooled data from 8 studies of exenatide once weekly, Blonde and colleagues found that patients who lost the most weight with exenatide quartiles 1 and 2 experienced the greatest reductions in LDL-C, total cholesterol, and TGs, and the greatest increases in HDL-C [ 67 ].
The sodium glucose co-transporter 2 SGLT2 inhibitors canagliflozin, dapagliflozin, and empagliflozin are the newest class of antihyperglycemic agents. They lower blood glucose levels by reducing renal glucose reabsorption, resulting in increased urinary glucose excretion. In addition, SGLT2 inhibitors are associated with reductions in body weight and total fat mass i.
The clinical relevance of such small changes affecting CVD risk has not yet been shown. The first CV safety trial of this drug class, with a relatively short median duration of 3. As a highly selective bile acid sequestrant BAS , colesevelam was first indicated as monotherapy and combination therapy to lower LDL-C levels and CVD risk, and was later indicated for decreasing blood glucose.
Its effects on bile acid pool composition, farnesoid X receptor-mediated alterations in hepatic glucose production and intestinal glucose absorption, influences on peripheral insulin sensitivity, incretin effects, and energy use may all contribute to glucose regulation, with a modest reduction in A1C of 0.
Therefore, combination therapies are recommended since clinically significant reduction of ASCVD risk is not likely to be achieved using monotherapy. Bromocriptine-QR is a quick-release formulation of bromocriptine mesylate. When added to antihyperglycemic therapy, bromocriptine-QR can provide significant improvement in glycemic control relative to placebo 0. This inhibition dramatically reduces the postprandial glycemic peaks and overall postprandial blood glucose levels, resulting in a moderate 0.
In a meta-analysis of placebo-controlled trials, acarbose did not significantly alter total cholesterol levels, but was associated with reductions in TG and increases in HDL-C levels [ 37 ]. In a multicenter, open-label, randomized controlled trial of acarbose compared with nateglinide in Chinese patients with T2DM, neither drug had significant effects on total cholesterol, HDL-C, LDL-C, or non-HDL-C levels; however, acarbose was associated with significantly greater reductions in fasting and postprandial TG levels compared with nateglinide [ 87 ].
Studies suggest that such reductions in CV risk are related to improvements in postprandial endothelial function [ 89 , 90 ]. Many patients with T2DM are often treated with insulin early in the disease process, in spite of the availability of multiple classes of antidiabetic agents with extremely low risks of hypoglycemia.
Direct insulin-related positive effects on the lipid profile include reductions in TG levels, most apparent with more dramatic improvement of glycemic control, along with increases in HDL-C levels; LDL-C levels remain typically unaffected [ 44 , 91 ].
The latest guidelines from the US Eighth Joint National Committee JNC 8 recommend the use of thiazide diuretics, angiotensin-converting enzyme ACE inhibitors, angiotensin receptor blockers ARBs , or calcium antagonists as first-line treatment of patients with hypertension, including those with diabetes [ 92 ]. Thiazide diuretics lead to dose-dependent increases in cholesterol levels without altering HDL-C levels [ 94 , 95 ].
Calcium antagonists do not appear to affect the lipid profile [ 94 , 98 ], although some evidence suggests that they might enhance TG removal [ 99 ]. The available data on the effect of ACE inhibitors on lipid profiles are inconsistent.
In the past, it was believed that ACE inhibitors had no effects on the lipid profile [ , ]; however, newer data suggest that some ACE inhibitors could have favorable effects on the lipid profile and atherosclerotic changes [ ], significantly lowering serum LDL-C and TG levels, and increasing HDL-C levels [ , ].
In general, ARBs also tend to lower apo B levels, while only losartan and valsartan have been shown to significantly decrease TG levels [ 95 ].
Treatment with ARBs may therefore positively impact CVD risk through blood pressure reduction and positive effects on the plasma lipid profile [ ]. In the case of propranolol, none of the associated lipid changes were considered to be strongly predictive of coronary events or mortality [ ].
In studies, use of the gastrointestinal lipase inhibitor orlistat has consistently been associated with reductions in LDL-C levels, while TG and HDL-C levels have either been reduced or not significantly changed when compared with placebo [ — ].
No consistent changes have been observed with the use of the selective serotonin-2C RA lorcaserin; TG and LDL-C levels remained unchanged or showed a slight reduction, whereas HDL-C levels increased slightly in some cases [ — ]. Relatively few data exist on the effects of antibiotics on lipid levels, although some changes have been observed in small studies. Metronidazole has been associated with a significant reduction in LDL-C levels, while ciprofloxacin has been linked to an increase in HDL-C levels [ , ].
In both cases, these effects were attributed to changes in the gastrointestinal flora as a result of antibiotic use. Although little information is available on the effects of these analgesics on the lipid profile, frequent use of NSAIDs or acetaminophen has been associated with a significantly increased risk of CV events [ ], with nonaspirin acetylsalicylic acid NSAIDs increasing the chance of a heart attack or stroke.
Aspirin is a more selective COX-1 inhibitor that has been shown to slightly decrease TG levels [ , ] and have moderate benefits on CVD-related factors, reducing the risk of stroke but not CHD [ ].
Furthermore, CKD is associated with dyslipidemia, which can, in some settings, be profound [ ]. Many oral contraceptives are associated with a negative impact on the lipid profile.
Second-generation oral progestogen contraceptives e. In contrast, third-generation progestogens e. In women taking oral conjugated estrogen combined with DMPA, no CV benefit has been observed in large randomized clinical trials of primary [ ] or secondary prevention [ , ]. The expected ASCVD benefit of oral combination HRT may have been offset by other effects, such as an increase in clotting factors and consequent elevated risk of thromboembolism.
Glucocorticoids, such as prednisone, are key therapies in the treatment of asthma and other inflammatory conditions. Thus, prolonged use of these medications can negatively impact the lipid profile and ASCVD risk factors [ 95 , ]. Vitamin D deficiency is associated with an unfavorable lipid profile in cross-sectional analyses, but correcting for a deficiency does not translate into clinically meaningful changes in lipid concentrations [ ].
Dietary supplementation with oils high in polyunsaturated fatty acids PUFAs has been shown to have favorable effects on serum lipid profiles in patients with T2DM or metabolic syndrome [ ]. Many medications widely prescribed for patients with T2DM influence, to varying degrees, selected components of the routine lipid profile i. While some effects may be significant, many medications are associated with relatively small changes in the lipid profile and are therefore unlikely to affect ASCVD risk by themselves.
However, the cumulative effect in patients taking multiple medications may be significant and should not be overlooked. The net effects of these medications on the lipid profile, in addition to effects on other factors related to CV health, should be anticipated, and their overall potential impact on ASCVD risk should be considered.
Therefore, clinicians can help to ensure optimal care and avoid putting patients at unnecessary risk by performing ongoing lipid-panel monitoring, taking into account potential effects of commonly prescribed medications. Ultimately, lifestyle recommendations and lipid-lowering agents are required to target atherogenic cholesterol and achieve the appropriate goals determined by the absolute risk for an individual, especially those with a relatively higher absolute risk i.
World Health Organization. Cardiovascular diseases CVDs. Accessed 10 May Endocr Pract. PubMed Article Google Scholar. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1—full report.
J Clin Lipidol. Lipoprotein management in patients with cardiometabolic risk: consensus statement from the American Diabetes Association and the American College of Cardiology Foundation. Diabetes Care. Diabetes and all-cause and coronary heart disease mortality among US male physicians. Arch Intern Med. The impact of diabetes mellitus on mortality from all causes and coronary heart disease in women: 20 years of follow-up.
Residual macrovascular risk in what have we learned? Cardiovasc Diabetol. Glycemic control and excess mortality in type 1 diabetes.
N Engl J Med. Excess mortality among persons with type 2 diabetes. Association of cardiometabolic multimorbidity with mortality. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: part I. Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol. J Intern Med. Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor.
Am J Cardiol. Drug-induced lipid changes: a review of the unintended effects of some commonly used drugs on serum lipid levels. Drug Saf. Eur Heart J. Unintended positive and negative effects of drugs on lipoproteins. Curr Opin Lipidol. Impact of diabetes on cardiovascular disease risk and all-cause mortality in older men: influence of age at onset, diabetes duration, and established and novel risk factors.
Insulin resistance and hyperinsulinemia in individuals with small, dense low density lipoprotein particles. J Clin Invest. Ovalle F. Cardiovascular implications of antihyperglycemic therapies for type 2 diabetes.
Clin Ther.
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