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Exploring Glycemic Challenges With Experts in T2DM

Exploring Guidelines and Opportunities for Advancing Type 2 Diabetes Therapy

Discover, alongside Dr. Vivian Fonseca, what the ADA and AACE guidelines recommend regarding titration and intensification of treatment for type 2 diabetes patients who are not meeting their glycemic targets.

Title: Exploring Guidelines and Opportunities for Advancing Type 2 Diabetes Therapy

I’m Dr. Fonseca, a practicing endocrinologist in New Orleans. Guidelines developed by the ADA and AACE encourage us to act when glycemic targets are not met or sustained over a period of time.

While individualized therapy is emphasized, as the guidelines state, many patients may need treatment intensification to meet their glycemic goals and prevent damage caused by persistent hyperglycemia.

Furthermore, treatment intensification may help us address some of the underlying physiologic abnormalities of this complex disease.

Let’s look at the guidelines themselves. ADA and AACE provide algorithms that suggest varied treatment options for patients with differing needs. This reflects how different each patient’s treatment journey can be.

There are similarities between these 2 guidelines. Both recommend lifestyle changes for all patients with type 2 diabetes. Both endorse metformin for initial therapy once patients require pharmacotherapy. And when patients no longer meet their individual A1C targets, both guidelines move them from dual therapy to triple therapy, and then eventually to regimens using insulin-based combination therapy.

Although the ADA and AACE guidelines are generally similar, they are not identical. They differ, for example, in their recommended A1C target. Setting such a target must balance several individual needs like reducing the threat of hypoglycemia while managing the risk of the complications that accompany hyperglycemia.

AACE aims for an A1C target of 6.5% or below, in general, for non-pregnant, healthy adults, while the ADA aims for a general target lower than 7.0%. However, both recommend individualization of goals, based on a number of patient-related factors.

Regardless of the A1C target set for a patient—6.5%, 7.0%, or some other individualized level, treatment intensification may be essential in some patients to achieve their glycemic goals. The ADA recommends that all patients have their A1C tested at least twice a year. They further recommend quarterly testing for patients who are not meeting their glycemic goals or have changed their regimen. AACE recommends testing every 3 months until multiple disease measures are stabilized. Treatment intensification is recommended once A1C exceeds a patient’s target levels.

Unfortunately, intensification is commonly delayed, which means that many patients may remain above their A1C target for prolonged periods, often for years.

In spite of the 3-month evaluation recommended by the guidelines, one study found that delays to treatment intensification took over 6 years for patients in actual clinical practice.

Failing to meet glycemic targets may increase the risk of microvascular and macrovascular complications.

Treatment intensification may also offer the opportunity to address the complexity of the disease. Type 2 diabetes involves the progressive decline and loss of insulin secretion, as well as reduced sensitivity to insulin.

But this oversimplifies the scope of the physiologic abnormalities that accompany the disease, because glucose control involves multiple organ systems. This collection of pathophysiologic abnormalities contributing to hyperglycemia is sometimes referred to as the “Ominous Octet.”

Among the diverse array of treatments available today, however, we have options that address each of these abnormalities.

Treatment intensification may involve adding therapies and/or using them together. In fact, one of the founding principles of the AACE guidelines is that combination therapy is usually required, and should involve agents with different mechanisms of action.

In practice, the AACE and ADA guidelines both address the complexity of diabetes by endorsing combinations of oral and combinations of injectable therapies. Many of these regimens employ therapies with different modes of action. In addition to reducing A1C, these regimens address multiple pathophysiologic abnormalities.

References: 1. ADA standards of medical care in diabetes–2016. Diabetes Care. 2016;39(suppl 1):S1-S112. 2. Garber AJ, Abrahamson MJ, Barzilay JI, et al; American Association of Clinical Endocrinologists; American College of Endocrinology. Consensus statement by the American Association of Clinical Endocrinologists and the American College of Endocrinology on the comprehensive type 2 diabetes management algorithm—2016 executive summary. Endocr Pract. 2016;22(1):84-113. doi:10.4158/EP151126.CS. 3. DeFronzo RA, Eldor R, Abdul-Ghani M. Pathophysiologic approach to therapy in patients with newly diagnosed type 2 diabetes. Diabetes Care. 2013;36(suppl 2):S127-S138. 4. Khunti K, Wolden ML, Thorsted BL, et al. Clinical inertia in people with type 2 diabetes. Diabetes Care. 2013;36(11):3411-3417. doi:10.2337/dc13-0331. 5. Ferrannini E, DeFronzo RA. Impact of glucose-lowering drugs on cardiovascular disease in type 2 diabetes. Eur Heart J. 2015;36(34):2288-2296. doi:10.1093/eurheartj/ehv239.