Second-Line Agents for Glycemic Control for Type 2 Diabetes: Are Newer Agents Better?

Zhang, Yuanhui; McCoy, Rozalina G.; Mason, Jennifer; Smith, Steven A.; Shah, Nilay D.; Denton, Brian T.

doi:10.2337/dc13-1901

Cited by 57 publications

(53 citation statements)

References 34 publications

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“…Another analysis performed on 39 randomized controlled trials involving 17 860 individuals, showed that glucagon-like peptide-1 (GLP-1) analogues led to a greater decrease in HbA1c compared with SUs, glinides, thiazolidinediones, α-glucosidase inhibitors and DPP-4 inhibitors [75]. Aiming to assess the benefits and harms of commonly used antihyperglycaemic treatment regimens, Zhang et al [76] recently developed a new population-based glycaemic control Markov model that simulates natural variation in HbA1c progression, and showed that when metformin monotherapy was intensified with SUs, DPP-4 inhibitors, GLP-1 receptor agonist or insulin, all regimens resulted in similar life-years and quality-adjusted life-years, regardless of the glycaemic control goal.Both pooled analysis and randomized clinical trials confirm that DPP-4 inhibitors provide a reasonable therapeutic alternative for elderly people with diabetes, as they lead to a significant improvement in glycaemic control, have a safety profile that is similar to placebo, are potentially better tolerated with respect to metformin, and are associated with a low risk of hypoglycaemia at least while used in monotherapy or in combination with insulin sensitizers. This view has also been confirmed by the results of the meta-analysis carried out by Schwarz [77].…”

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confidence: 99%

Dipeptidyl peptidase‐4 inhibitors can minimize the hypoglycaemic burden and enhance safety in elderly people with diabetes

Avogaro

Dardano

Kreutzenberg

et al. 2014

Diabetes Obesity Metabolism

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The prevalence of type 2 diabetes mellitus (T2DM) among elderly people is increasing. Often associated with disabilities/comorbidities, T2DM lowers the chances of successful aging and is independently associated with frailty and an increased risk of hypoglycaemia, which can be further exacerbated by antihyperglycaemic treatment. From this perspective, the clinical management of T2DM in the elderly is challenging and requires individualization of optimum glycaemic targets depending on comorbidities, cognitive functioning and ability to recognize and self-manage the disease. The lack of solid evidence-based medicine supporting treatment guidelines for older people with diabetes further complicates the matter. Several classes of medicine for the treatment of T2DM are currently available and different drug combinations are often required to achieve individualized glycaemic goals. Many of these drugs, however, carry disadvantages such as the propensity to cause weight gain or hypoglycaemia. Dipeptidyl peptidase-4 (DPP-4) inhibitors, a recent addition to the pharmacological armamentarium, have become widely accepted in clinical practice because of their efficacy, low risk of hypoglycaemia, neutral effect on body weight, and apparently greater safety in patients with kidney failure. Although more information is needed to reach definitive conclusions, growing evidence suggests that DPP-4 inhibitors may become a valuable component in the pharmacological management of elderly people with T2DM. The present review aims to delineate the potential advantages of this pharmacological approach in the treatment of elderly people with T2DM. Keywords: comorbidities, diabetes treatment, frailty, hypoglycaemia, incretin therapy, renal impairment Date submitted 20 December 2013; date of first decision 3 February 2014; date of final acceptance 20 May 2014 IntroductionIt is well known and has been amply shown that the global population with diabetes has been growing over the past decades and that it will continue to increase even further in the near future [1]. What is less appreciated is that diabetes, particularly in the Western Hemisphere, will become a major problem in the elderly population. Life expectancy has increased in the general population as well as in those with diabetes [1]. More people with diabetes will grow older and more people will develop diabetes later in life. The result will be an increase in the prevalence of diabetes in the elderly. The number of people with diabetes aged ≥65 years is expected to double between 2010 and 2015, with the actual number rising from 55 to almost 130 million [2].Diabetes in the elderly is often associated with disabilities, and >70% of the elderly people with type 2 diabetes mellitus (T2DM) have some degree of impaired physical activity [3]. Elderly subjects, especially those with diabetes, tend to be frailer and experience weight loss, to be more prone to exhaustion, to have lower energy expenditure, slower gait speed and Correspondence to: Angelo Avogaro, MD, PhD, Department of Medi...

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confidence: 99%

Dipeptidyl peptidase‐4 inhibitors can minimize the hypoglycaemic burden and enhance safety in elderly people with diabetes

Avogaro

Dardano

Kreutzenberg

et al. 2014

Diabetes Obesity Metabolism

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“…We are grateful for the comments from Messori and Bellia (1) and those of Bae et al (2) regarding our article (3). We hope the following response will clarify the questions they raised.…”

Section: Response To Comments On Zhang Et Almentioning

confidence: 82%

Response to Comments on Zhang et al. Second-Line Agents for Glycemic Control for Type 2 Diabetes: Are Newer Agents Better? Diabetes Care 2014;37:1338–1345

et al. 2014

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We are grateful for the comments from Messori and Bellia (1) and those of Bae et al. (2) regarding our article (3). We hope the following response will clarify the questions they raised.Messori and Bellia (1) pointed out that the incremental cost-effectiveness ratio (ICER) is preferred over the absolute cost-effectiveness ratio. We agree, and it is worth noting that Fig. 1 in our article provides complete details about the expected quality-adjusted life-years (QALYs) prior to first events and the expected medication costs under all treatment regiments. As such, it subsumes ICER estimates. Admittedly, the readers must calculate them from the graph and therefore we provide the estimates for the glycemic control goal of HbA 1c ,7% here. For males, for regimens T1-T4 the ICERs in units of $/QALY are 10, 369, 11,062, 11,277, 11,144, respectively. For females, for regimens T1-T4 the ICERs are 9, 310, 9,865, 10,043, 9,933, respectively. Messori and Bellia also express confusion over the computation of life-years to first event. To clarify, our reported results are based on a median diagnosis age between 54 and 55 years. The lifeyears to first event are the sum of time to diagnosis and the time from diagnosis to first event, where the latter is computed using our model. Bae et al. question an apparent assumption in our model that "underlying HbA 1c fluctuation at baseline remains constant throughout the patient's life" (2). However, we did not assume a constant baseline; we assumed a linear increasing trend in HbA 1c , consistent with other published glycemic control models (4,5).Bae et al. suggested the use of treatment effect estimates, based on realworld data, is a major limitation. We take the contrary perspective, i.e., that this is a strength of our study, as realworld data accounts for potential lack of adherence and other behavioral factors that may not be present in the ideal setting of a randomized controlled trial (RCT). Of course, we also recognize the merit of RCTs in limiting bias, and for this reason we reported results based on treatment effects reported in RCTs. As readers can see from our results, these do not change our main conclusions.Bae et al. propose the use of a longer time window for measuring the effect of medications. In our analysis, we found no evidence that a longer time window would make a significant difference. Compared with the 3-month time window used in our article, the use of 6-and 12-month time windows before and after treatment initiation resulted in similar or decreased treatment effects for the newer medications. Bae et al. also suggested the use of propensity score methods to account for possible confounding. This would be interesting to explore in theory, but in practice there are likely a number of unmeasured confounders. Fortunately, our sensitivity analysis based on RCT estimates obviates all of these concerns.Bae et al. fairly criticize the fact that the cost of hypoglycemia was not included in the model. As they pointed out, we adjusted for hypoglycemia outcomes, but n...

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“…However, the cost of this benefit was less in patients who were treated with sulfonylureas. 22 These drugs were also associated with a longer interval until insulin was required than was the case when other oral agents were used. These findings are being translated into potential revisions of guidelines used by care providers.…”

Section: Expanding Through Research Translation and Innovationmentioning

confidence: 99%

Optum Labs: Building A Novel Node In The Learning Health Care System

et al. 2014

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Unprecedented change in the US health care system is being driven by the rapid uptake of health information technology and national investments in multi-institution research networks comprising academic centers, health care delivery systems, and other health system components. An example of this changing landscape is Optum Labs, a novel network "node" that is bringing together new partners, data, and analytic techniques to implement research findings in health care practice. Optum Labs was founded in early 2013 by Mayo Clinic and Optum, a commercial data, infrastructure services, and care organization that is part of UnitedHealth Group. Optum Labs now has eleven collaborators and a database of deidentified information on more than 150 million people that is compliant with the Health Insurance Portability and Accountability Act (HIPAA) of 1996. This article describes the early progress of Optum Labs. The combination of the diverse collaborator perspectives with rich data, including deep patient and provider information, is intended to reveal new insights about diseases, treatments, and patients' behavior to guide changes in practice. Practitioners' involvement in agenda setting and translation of findings into practical care innovations accelerates the implementation of research results. Furthermore, feedback loops from the clinic help Optum Labs expand on successes and give quick attention to challenges as they emerge.

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Second-Line Agents for Glycemic Control for Type 2 Diabetes: Are Newer Agents Better?

Cited by 57 publications

References 34 publications

Dipeptidyl peptidase‐4 inhibitors can minimize the hypoglycaemic burden and enhance safety in elderly people with diabetes

Dipeptidyl peptidase‐4 inhibitors can minimize the hypoglycaemic burden and enhance safety in elderly people with diabetes

Response to Comments on Zhang et al. Second-Line Agents for Glycemic Control for Type 2 Diabetes: Are Newer Agents Better? Diabetes Care 2014;37:1338–1345

Optum Labs: Building A Novel Node In The Learning Health Care System

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