Few health crises have been as predictable as the unfolding obesity pandemic. Clinical and public health services remain the front line of efforts to reduce the burden of obesity. While a range of clinical practice guidelines exist, the need for clinical interventions exceeds the capacity of health systems to provide care for those affected with obesity, and routine clinical practices fall far short of guidelines recommendations even in high-income countries. In this manuscript, we discuss current recommendations regarding obesity interventions and key challenges facing global health systems in managing the health needs of people with obesity. Improving the provision of obesity-related health care is a considerable challenge and will require changing existing perceptions of obesity as a matter of personal failure to its recognition as a disease, innovative approaches to health system reform, clinician capacity building and implementation support, a focus on prevention, and wise resource allocation. Leadership from governments, the medical profession, and patient and community groups to address the issues raised in this manuscript is urgently needed to address the growing health concern.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/obr.12872

The challenge for global health systems in preventing and managing obesity.

The pharmacological management of diabetes in older people is complex and challenging. It requires a comprehensive understanding of the individual beyond the diabetes itself. Through the ageing years, the older individual presents with diabetes-related and non-related comorbidities and complications, develops functional limitations and psychological issues, and may lack social support and access to care. A disturbance in these categories, known as the four geriatric domains, will negatively affect diabetes self-management and self-efficacy, leading to poor outcomes and complications. Furthermore, older people with diabetes may be more interested in the management of other chronic conditions such as pain or impaired mobility, and diabetes may be lower in their list of priorities. Proper education must be provided to the older individual and caregivers, with continuous monitoring and counselling, especially when pharmacological interventions offer risks of side effects, adverse reactions and interactions with other medications. Informed shared medical decisions will help to improve adherence to the regimen; however, such discussions ought to be based on the best evidence available, which is unfortunately limited in this age group. We performed a review focused on pharmacological agents and summarize current evidence on their use for the treatment of diabetes in older people. We encourage clinicians to investigate and incorporate the four geriatrics domains in the selection and monitoring of these agents.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/dom.12362

Pharmacological treatment of diabetes in older people.

Hispanics are the fastest growing ethnic minority in the USA. Among Hispanics, lack of hypertension awareness and lack of effective blood pressure (BP) control are problematic, as are higher incidence rates of hypertension-related co-morbidities compared with non-Hispanic populations. Moreover, there are currently no hypertension treatment guidelines that address the unique characteristics of this ethnic group. This article discusses ethnic differences in hypertension and cardiovascular risk factors and reviews the literature on the efficacy of antihypertensive agents in Hispanic patients, with a focus on the role of renin-angiotensinaldosterone system (RAAS) inhibition in the management of hypertension in these patients. Hypertension in Hispanic patients can be challenging to manage, in part because this population has a higher prevalence of obesity, diabetes, and metabolic syndrome compared with non-Hispanic whites. The presence of these comorbidities suggests that RAAS-inhibitor-based therapies may be particularly beneficial in this population. However, few studies have evaluated the efficacy of antihypertensive treatments in Hispanic patients. Two outcomes studies in hypertensive patients have shown the benefits of treating Hispanic patients with antihypertensive therapy and included RAAS inhibitors as part of the treatment regimen. In addition, BP-lowering trials have shown the antihypertensive efficacy of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and direct renin inhibitors, although data on the latter are more limited. Additional studies are needed to more thoroughly evaluate the effects of RAAS inhibitors (and other drug classes) on outcomes and BP lowering in the Hispanic hypertensive population.

https://link.springer.com/content/pdf/10.2165%2F11631520-000000000-00000.pdf

Epidemiology and management of hypertension in the hispanic population: A review of the available literature

Hypertension is a serious public health concern with inadequate control of blood pressure (BP) worldwide. Contributing factors include low efficacy of drugs, underuse of combination therapies, irrational combinations, physicians' therapeutic inertia and poor adherence to treatment. Current guidelines recommend the use of initial (dual) combination therapy in high-risk patients for immediate BP response, better short- and long-term BP control, and continued/improved patient adherence. This article aims to review the existing evidence of triple-combination therapies with respect to efficacy, safety and adherence to treatment. It is estimated that three drugs are required to achieve BP control in approximately one-fourth to one-third of patients. Randomised controlled trials (RCTs) have shown that triple combinations of amlodipine/valsartan/hydrochlorothiazide, amlodipine/olmesartan/hydrochlorothiazide and amlodipine/telmisartan/hydrochlorothiazide produce greater BP reductions, with greater proportions of patients achieving BP control compared with dual therapies. Further evidence also demonstrates that triple-combination therapy is efficacious for moderate to severe hypertension, with substantial additional BP reduction over dual regimens. Both RCTs and post-marketing observational studies have shown consistent and comparable efficacy in both the general population and high-risk hypertensive subgroups. Triple therapies are generally well tolerated with adverse event profiles similar to dual regimens. In addition, fixed-dose combinations used as single pill improve patient adherence leading to better long-term BP control. Depending on regional circumstances, they may also be cost effective. Thus, single-pill triple combinations of different classes of drugs with complementary mechanisms of action help to treat patients to goal with improved efficacy and better adherence to treatment.

Triple-combination therapy in the treatment of hypertension: a review of the evidence

Hypertension (HTN) is a worldwide health problem and a major preventable risk factor for cardiovascular (CV) events. Achieving an optimal blood pressure (BP) target for patients with HTN will often require more than one BP-lowering drug. Combination therapy is not only needed, but also confers many advantages such as better efficacy and a better tolerability. A better compliance and simplicity of treatment is noted with the single-pill combination (SPC). In addition, for those patients who do not achieve BP target when receiving dual combinations, triple SPCs are now available, and their efficacy and safety have been tested in large clinical trials. BP-lowering drugs used in combination therapy should have complementary mechanisms of action, leading to an additive BP-lowering effect and improvement in overall tolerability, achieved by decreasing the incidence of adverse effects. On the basis of large, outcome-driven trials, preferred dual combinations include an angiotensin receptor antagonist (ARB) or an angiotensin converting enzyme inhibitor (ACEI) combined with a calcium channel blocker (CCB), or an ARB or ACEI combined with a diuretic. Acceptable dual combinations include a direct rennin inhibitor (DRI) and a CCB, a DRI and a diuretic, a beta-blocker and a diuretic, a CCB and a diuretic, a CCB and a beta-blocker, a dihydropyridine CCB and a non-dihydropyridine CCB, and a thiazide diuretic combined with a potassium-sparing diuretic. Some combinations are not recommended and may even be harmful, such as dual renin angiotensin aldosterone system inhibition. Currently available triple SPCs combine a renin angiotensin aldosterone system inhibitor with a CCB and a diuretic. Combination therapy as an initial approach is advocated in patients with a systolic BP more than 20 mmHg and/or a diastolic BP more than 10 mmHg above target and in patients with high CV risk. In addition, using SPCs has been stressed and favored in recent international guidelines. Recently, triple SPCs have been approved and provide an attractive option for patients not achieving BP target on dual combination. The effect of such a strategy in the overall management of HTN, especially on further reducing the incidence of CV events, will have to be confirmed in future clinical and population-based studies.

/pdf/current-perspectives-on-combination-therapy-in-the-3df1a38q8i.pdf

Current perspectives on combination therapy in the management of hypertension

Minority patients with hypertension generally require combination therapy to reach blood pressure (BP) goals. We examined the BP-lowering efficacy and safety of combination aliskiren/amlodipine therapy in self-identified minority patients in the United States with stage 2 hypertension and the impact of adding hydrochlorothiazide (HCTZ) to this combination. In this 8-week double-blind study, 412 patients were randomized to receive aliskiren/amlodipine (150/5 mg) or amlodipine (5 mg) with forced titration up to aliskiren/amlodipine/HCTZ (300/10/25 mg) or aliskiren/amlodipine (300/10 mg), respectively. Overall, mean age was 55.2 years, mean body mass index was 32 kg/m(2), 62.3% were black, 28.2% were Hispanic/Latino, and 69.1% had metabolic syndrome. Mean sitting systolic blood pressure (MSSBP), the primary efficacy outcome, was reduced from 167.1 mm Hg at baseline to 130.7 mm Hg at week 8 with aliskiren/amlodipine/HCTZ and from 167.4 mm Hg to 137.9 mm Hg with aliskiren/amlodipine (P < .0001 between groups). At week 8, BP goal (<140/90 mm Hg) was achieved in 72.6% and 53.2% of patients in the two treatment groups, respectively (P < .0001). Adverse events were experienced by 34.2% and 40.2%, respectively. Combination aliskiren/amlodipine therapy was effective in treating these high-risk patients but inclusion of HCTZ provided greater antihypertensive efficacy. Both treatments were similarly well tolerated.

Efficacy and safety of aliskiren-based dual and triple combination therapies in US minority patients with stage 2 hypertension.

Initial multiple drug therapy for hypertension achieves greater and quicker reductions and higher blood pressure (BP) control rates than monotherapy. This 8-week, prospective, multicenter, randomized, double-blind study compared the efficacy and safety of the initial combination of aliskiren/amlodipine with amlodipine monotherapy in African Americans with stage 2 hypertension. After a 1- to 4-week washout, patients received aliskiren/amlodipine 150/5 mg or amlodipine 5 mg for 1 week and then were force-titrated to aliskiren/amlodipine 300/10 mg or amlodipine 10 mg for 7 weeks. At week 8, greater reductions in mean sitting systolic BP were obtained with aliskiren/amlodipine (n = 220) than with amlodipine (n = 223) (least squares mean change [standard error of the mean], -34.1 [1.14] mm Hg vs -28.9 [1.12] mm Hg; P<.001). Ambulatory and central BP measures were consistent with clinic BP findings, although these were conducted in a small subset of patients (n = 94 in ambulatory BP monitoring substudy and n = 136 for central BP). More patients achieved goal BP (<140/90 mm Hg) with aliskiren/amlodipine than with amlodipine at week 8 (57.3% vs 48.0%; P = .051). Both treatment groups had similar adverse event rates (35.0% and 32.7%, respectively). The most common adverse events were peripheral edema (7.7% with aliskiren/amlodipine and 9.0% with amlodipine), headache, fatigue, and nausea. The combination of aliskiren/amlodipine reduced peripheral, ambulatory, and central BP more than amlodipine alone with similar tolerability in African Americans with stage 2 hypertension.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1751-7176.2011.00483.x

Comparative efficacy and safety of combination aliskiren/amlodipine and amlodipine monotherapy in African Americans with stage 2 hypertension.

The increasing prevalence of type 2 diabetes provides impetus for both development of new drugs to improve glycemic control and for reconsideration of treatment strategies with existing agents. Combination therapy with complementary drug classes that act on different aspects of glycemic control has been a particularly effective strategy. This work reviews the published literature reporting efficacy and safety/tolerability of nateglinide, a rapid-onset insulinotropic agent with a predominant effect to reduce postprandial glucose, when combined with metformin, a first-line agent that suppresses hepatic glucose production and thereby reduces fasting plasma glucose. The nateglinide/metformin combination has consistently been found to be both efficacious and well tolerated, whether given as initial combination therapy in drug-naive patients or when added to metformin monotherapy. Maximum efficacy (Δ glycosylated hemoglobin [HbA1c]= −1.4% to −1.9%, sustained for up to 2 years of treatment) was seen in studies of drug-naive patients in whom pharmacotherapy was initiated with the combination of nateglinide and metformin, and modest reductions in HbA1c (Δ = −0.5% to −1.2%, sustained for up to 24 weeks) were found when nateglinide was added to ongoing metformin monotherapy.

Conclusion: the combination of nateglinide and metformin provides a sustained degree of glycemic control not achievable with either agent given as monotherapy.

Marc Israel

Papers

Efficacy and safety of aliskiren-based dual and triple combination therapies in US minority patients with stage 2 hypertension.

Comparative efficacy and safety of combination aliskiren/amlodipine and amlodipine monotherapy in African Americans with stage 2 hypertension.

Safety and efficacy of nateglinide/metformin combination therapy in the treatment of type 2 diabetes.

Gaps in guideline-based lipid-lowering therapy for secondary prevention in the united states: a nationwide analysis of 227,824 patients

Lipid-Lowering Therapy for Primary Prevention of Cardiovascular Disease: A Nationwide Analysis of 440,721 Patients