Clinical Updates in Type 2 Diabetes

Individualizing T2DM Treatment With GLP-1 Receptor and Basal Insulin Analogs In the absence of contraindications or unacceptable tolerability issues, metformin is generally accepted as the first-line medication of choice for newly diagnosed T2DM.3,4 This consensus recommendation reflects metformin’s long history of efficacy and safety, relatively low cost, and published evidence linking metformin to modest weight loss and lower long-term risks of cardiovascular complications and mortality.3,4,14 However, to sustain adequate glycemic control as T2DM progresses, almost all patients require antihyperglycemic regimens that advance beyond recommended lifestyle modifications and maximally dosed metformin alone.

3,4 In fact, discussions of the potential benefits and risks of initiating therapy with multiple medications are warranted when untreated patients present with markedly elevated A1c levels. In the 2017 version of their comprehensive Standards in Medical Care in Diabetes, the American Diabetes Association (ADA) states that initial 2-drug regimens (ie, metformin plus a second agent) should be considered when A1c values are ≥9.0% in newly diagnosed T2DM cases or in other patients not currently taking antihyperglycemic medications.3 The ADA also makes the point that combinations of injectable therapies are appropriate initial regimens when A1c values are ≥10.0%, fasting plasma glucose levels are ≥300 mg/dL, or the patient is markedly symptomatic.3 The glycemic control algorithm published by the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) is more aggressive, noting that two-drug regimens are the preferred initial choice when patients enter treatment with A1c values ≥7.5%.4,15 Among the numerous possible combinations of antihyperglycemic classes and individual agents available to treat T2DM, many recent clinical trials and other peer-reviewed publications have focused on the potential benefits of coadministering glucagon-like peptide-1 (GLP-1) receptor agonists and basal insulin analogs.16,17 These efforts largely reflect the promise of simultaneously harnessing the robust glucose-lowering effects of both medication classes, while also taking advantage of safety profiles and secondary benefits observed in clinical trials with GLP-1 receptor agonists. In real-world practice, GLP-1 receptor agonist/basal insulin combination regimens will usually be only considered in patients for whom regimens containing an agent from 1 of the 2 injectable antihyperglycemic classes have failed to provide adequate glycemic control. This is also reflected in the prescribing information sheets for the 2 fixed-dose GLP-1 receptor agonist/basal insulin analog combination formulations approved by the US Food and Drug Administration (FDA) (Table 3.1).

If the clinician and patient agree that combining a GLP-1 receptor agonist and a basal insulin analog is the most attractive next step to achieve adequate glycemic control, the next step is to determine which particular combination is the best choice for that individual. This decision should be made based on published efficacy and safety evidence for the various combinations, patient preferences, previous assessment of treatment adherence, and consideration of unique aspects in the clinical profiles of the individual agents, information from regulatory agencies, and managed care constraints. For example, options for a given patient may at times be narrowed by insurance formularies or, in the case of albiglutide, the manufacturer’s decision to discontinue production within the next 9 months. Furthermore, as discussed in Chapter 2, the FDA’s specific indications differ on using the various GLP-1 receptor agonists with either basal or prandial insulin products, although this inconsistency primarily reflects whether data have been submitted for formal FDA review, rather than efficacy or safety concerns when “off-label” combinations are prescribed.

Clinicians can also consider the published results of numerous head-to-head trials with GLP-1 receptor agonists, many of which have revealed efficacy and/or tolerability differences.20,21 Major themes emerging 25