Combination therapy was well tolerated and resulted in significantly greater BP reductions and attainment of BP goals compared with monotherapy in patients with stage 2 hypertension. This evidence supports the recommendation of combination therapy as first-line treatment in stage 2 hypertension.

Colesevelam’s glucose-lowering mechanism of action is not completely understood. Clinical trials of colesevelam suggest that its mechanism, and often adverse effects, differ from those of other oral antidiabetes drugs. Colesevelam does not affect insulin sensitivity (unlike thiazolidinediones), insulin secretion (unlike sulfonylureas and meglitinides), or early insulin response or glucagon (unlike dipeptidyl peptidase-4 inhibitors). Colesevelam may have some effect on glucose absorption, but likely via a different mechanism than α-glucosidase inhibitors. Colesevelam and metformin have similarities regarding hepatic glucose production, but divergent effects on gluconeogenesis versus glycogenolysis, suggesting differing mechanisms of drug action for improving glycemic control. Colesevelam is thought to be a portal glucagon-like peptide-1 (GLP-1) secretagogue with primarily hepatic effects. Bile acid binding by colesevelam leads to TGR5 activation, increased secretion of GLP-1 or other incretins, and inhibition of hepatic glycogenolysis. Colesevelam’s mechanism of action appears to be atypical of other antidiabetes medications, making it a potentially suitable component of many combination regimens in the treatment of type 2 diabetes.

Hyperlipidemia is associated with an increased risk of cardiovascular events; reducing low-density lipoprotein cholesterol (LDL-C), the primary target for cholesterol-lowering therapy, lowers the risk for such events. Although bile acid sequestrants were the first class of drugs to show a mortality benefit related to LDL-C lowering, statins are now considered first-line pharmacological therapy for reducing LDL-C levels because of their potency and their remarkable record of successful outcomes studies. Nevertheless, a substantial proportion of patients do not achieve LDL-C goals with statin monotherapy. In addition, because of adverse effects (primarily myopathy), some patients may be unwilling to use or unable to tolerate statin therapy at all or may not tolerate a full therapeutic statin dose. Also, statins may increase risk of new-onset diabetes in patients at high risk for diabetes. Thus, there remains a need for other lipid-lowering drugs to be used in combination with or in place of statins. The purpose of this article is to review available data from the literature on the use of colesevelam, a second-generation bile acid sequestrant, in combination with other lipid-lowering agents. Colesevelam has been studied in combination with statins, niacin, fibrates, and ezetimibe (including some three-drug combinations). An additive reduction in LDL-C was seen with all combinations. Other observed effects of colesevelam in combination with other lipid-lowering drugs include reductions in apolipoprotein (apo) B (with statins, fibrates, ezetimibe, statin plus niacin, or statin plus ezetimibe) and high-sensitivity C-reactive protein (with statins), and increases in apo A-I (with statins, ezetimibe, or statins plus niacin). Triglyceride levels remained relatively unchanged when colesevelam was combined with statins, fibrates, ezetimibe, or statin plus ezetimibe, and decreased with the triple combination of colesevelam, statin, and niacin. Colesevelam offset the negative glycemic effects of statins and niacin in subjects with insulin resistance or impaired glucose tolerance. Colesevelam was generally well tolerated when added to other lipid-lowering therapies in clinical trials, with gastrointestinal effects such as constipation being the predominant adverse events. Since colesevelam is not absorbed and works primarily in the intestine, it has a low potential for systemic metabolic drug–drug interactions with other drugs. Colesevelam has been shown to not interact with the lipid-lowering drugs lovastatin and fenofibrate; where interaction may be anticipated, separating dosing times by 4 h reduces the impact of any interaction. Available data confirms that colesevelam has additive cholesterol-lowering effects when used in combination with other lipid-lowering therapies. Furthermore, in some patient populations, the additional glucose-lowering effect of colesevelam may be beneficial in offsetting hyperglycemic effects of other lipid-lowering drugs.

Purpose The safety and efficacy of subcutaneous immune globulin 20% (human) solution (Ig20Gly) were demonstrated in clinical trials. However, real-world evidence of the tolerability of self-administered Ig20Gly in elderly patients is lacking. We describe real-world patterns of Ig20Gly usage for 12 months in patients with primary immunodeficiency diseases (PIDD) in the USA. Methods This retrospective chart review of longitudinal data from 2 centers included patients aged ≥ 2 years with PIDD. Ig20Gly administration parameters, tolerability, and usage patterns were assessed at initial and subsequent 6- and 12-month infusions. Results Of 47 enrolled patients, 30 (63.8%) received immunoglobulin replacement therapy (IGRT) within 12 months before starting Ig20Gly, and 17 (36.2%) started IGRT de novo. Patients were predominantly White (89.1%), female (85.1%), and elderly (aged > 65 years, 68.1%; median age = 71.0 years). Most adults received at-home treatment during the study, and most self-administered at 6 months (90.0%) and 12 months (88.2%). Across all time points, infusions were administered at a mean rate of 60–90 mL/h/infusion, using a mean of 2 sites per infusion, on a weekly or biweekly frequency. No emergency department visits occurred, and hospital visits were rare (n = 1). Forty-six adverse drug reactions occurred in 36.4% of adults, mostly localized site reactions; none of these or any adverse events led to treatment discontinuation. Conclusion These findings demonstrate tolerability and successful self-administration of Ig20Gly in PIDD, including elderly patients and patients starting IGRT de novo.