Insulin

Insulin is “the most potent glucose-lowering agent.” However, there are many factors to take into account in the decision to initiate insulin therapy and in the formulation selected. These include the patient’s level of motivation, cardiovascular and end-organ complications, age, general well-being, hypoglycemia risk, overall health status, and cost considerations. The authors note that patients taking two oral antihyperglycemic agents are less likely to reach their target A1C with the addition of a third, although adding a glucagon-like peptide-1 receptor agonist (GLP-1 RA) as a third agent may successfully lower A1C. If these patients require further agents to reach targets, a single dose of basal insulin would be appropriate. It is important to adjust the dosage at regular and fairly short intervals so as to balance achieving the glucose target while avoiding hypoglycemia.

Basal insulin analogs provide a flat serum insulin concentration for up to 24 hours, and are preferable to neutral protamine Hagedorn (NPH) insulin. Insulin analogues cause significantly less hypoglycemia than NPH. Newer basal insulin formulations (glargine U300 and degludec U100 and U200) have more prolonged and stable pharmacokinetic and pharmacodynamics than do glargine U100 and detemir. Premixed insulins provide less dosing flexibility and have also been associated with a higher frequency of hypoglycemic events, compared to basal and basal-bolus regimens. But it is a “reasonable compromise” to use these agents in patients who prefer simpler regimens. If glycemic goals are not sufficiently achieved with basal insulin, a GLP-1 RA, sodium glucose cotransporter-2 inhibitor (SGLT-2i), or a dipeptidyl peptidase 4 inhibitor (DPP-4i) may be added to the regimen.


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Blood Pressure

Hypertension in patients with T2D is associated with an increased risk of cardiovascular (CV) events. BP control must be individualized, but a target of <130/80 mm Hg is appropriate for most patients. In frail patients with complicated comorbidities, or who have adverse medication effects, a more intensive goal (<120/mm Hg) can be considered if the target can be reached safely and without adverse medication effects.

Some patients can achieve BP goals through lifestyle therapy, including weight loss, sodium restriction, moderation of alcohol intake, and physical exercise. If medication is needed, factors to take into account when selecting an antihypertensive agent can be found in Table 7. In general, angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor II blockers (ARBs), calcium channel blockers, beta-blockers, and thiazide diuretics are “favored choices for first-line treatment.” In patients with BP >150 mm Hg, it is unlikely that a single agent will be sufficient to achieve BP goal, so treatment should be initiated with two antihypertensives. However, an ARB/ACEI combination should be avoided, because it increases risk of renal failure and hyperkalemia.

Lipids

Patients with T2D have significantly increased risk of atherosclerotic cardiovascular disease (ASCVD). Controlling atherogenic cholesterol particle concentrations is “fundamental to prevention of macrovascular disease,” so early intensive management of dyslipidemia is necessary.

In stratifying risk for primary prevention of ASCVD, patients with diabetes are classified as “high risk,” “very high risk,” or “extreme risk” of developing ASCVD. Risk factors and targets are listed in Table 8. Statins are generally considered to be first-line therapy, unless contraindicated. Intensifying statin therapy can result in muscle-related adverse effects. Other lipid-modifying agents to be used in combination with maximally tolerated statins if lipid goals have not been reached include ezetimibe, proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors, colesevelam, fibrates, niacin, and omega-3 fatty acids.

Conclusion

The authors state that the algorithm “was developed to provide clinicians with a practical guide that considers the whole patient, their spectrum of risks and complications, and evidence-based approaches to treatment.”

References

1.      Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm – 2017 executive summary.  Endocr Pract. 2017 Jan 17. [Epub ahead of print]

2.      Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of clinical Endocrinologists and American College of Endocrinology on the comprehensive Type 2 diabetes management algorithm – 2016 executive summary. Endocr Pract. 2016;22(1):84-113.