Meeting News

Trial data highlight need for redefined guidelines for older adults with diabetes

PHILADELPHIA — Older adults with type 2 diabetes can derive meaningful cardiovascular and renal benefits from newer antihyperglycemic agents, and data from several large CV outcomes trials suggest that treatment guidelines for this population should be redefined to reflect such findings, according to a speaker here.

Richard E. Pratley

“We need to rethink treatment guidelines for older individuals to target CVD and renal outcomes, as we are doing in the general population,” Richard E. Pratley, MD, the Samuel E. Crockett chair in diabetes research and medical director of AdventHealth Diabetes Institute, told Endocrine Today. Older individuals with type 2 diabetes have very high rates of major adverse CV events; however, they tend to derive a similar benefit [with therapy] as do younger patients. In some cases, the benefit is greater.”

Diabetes in older adults is a growing health problem, Pratley said. Approximately 11% of the world’s population is aged at least 60 years; that number will double by 2050, he said. People with diabetes are living longer, and they are vulnerable to the traditional microvascular and macrovascular complications of diabetes, as well as mortality. Diabetes among older adults is also heterogenous; some have long-standing diabetes with associated complications, whereas others are newly diagnosed with or without end-organ complications at time of presentation, Pratley said.

“The risks for these groups are quite different, and our treatment approach should be quite different as well,” Pratley said.

Historically, these older patients with type 2 diabetes were excluded from clinical trials of new drugs, despite older individuals making up a substantial fraction of patients with diabetes, Pratley said.

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Older adults with type 2 diabetes can derive meaningful cardiovascular and renal benefits from newer antihyperglycemic agents, and data from several large CV outcomes trials suggest that treatment guidelines for this population should be redefined to reflect such findings.
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“The [FDA] requirement to conduct [CV outcomes trials] has changed all that,” Pratley said. “Forty percent to 50% of patients in CV outcomes trials are aged at least 65 years. We now have much better long-term data in this population.”

New focus needed

A new Endocrine Society Clinical Practice Guideline on the treatment of older adults with diabetes, published earlier this year, recommends individualized HbA1c treatment goals based on health status. Adults who are healthy with a longer remaining life expectancy should be treated to an HbA1c goal of less than 7.5%; those with very complex or poor health and a limited remaining life expectancy should be treated to an HbA1c goal of about 8.5%.

“However, these [guidelines] are really focused on glycemic goals,” Pratley said. “As with the general population, we feel they should be individualized based on a variety of factors, including things like hypoglycemia.”

Recent CV outcomes studies have revealed interesting data on large numbers of older adults who previously would not have been studied, Pratley said. The SAVOR-TIMI 53, EXAMINE, TECOS, CAROLINA and CARMELINA studies, which assessed DPP-IV inhibitors, included a combined 50,000 patients with type 2 diabetes, with a mean age of 61 to 66 years, he said. In SAVOR-TIMI 53, TECOS and CAROLINA, 14% of participants were aged at least 75 years. Similarly, across four CV outcomes trials assessing SGLT2 inhibitors — EMPA-REG, CANVAS, DECLARE-TIMI 58 and VERTIS-CV — the mean age of participants was 64 years. Trials for GLP-1 receptor agonists, including ELIXA, LEADER, SUSTAIN 6, EXSCEL, HARMONY, REWIND and PIONEER 6, included more than 56,000 patients with a mean age of 60 to 66 years.

“That is now thousands of patients who are elderly, who are at risk for CV disease, where we have good follow-up,” Pratley said. “This has never existed before.”

Target comorbidities

The data across these studies suggest a common theme, Pratley said: Older adults with diabetes overall did just as well on new antihyperglycemic agents as younger patients, and in some instances, they derived a greater CV or mortality benefit. In an age-stratified analysis of the LEADER trial, Pratley and colleagues observed that the HR for major adverse CV events in patients aged at least 75 years assigned liraglutide (Victoza, Novo Nordisk) was 0.7 (95% CI, 0.5-0.95) vs. 0.88 (95% CI, 0.76-1.02) in patients assigned the drug who were younger than 75 years.

“We need to redefine the targets in older individuals as we have done in the younger individuals, focusing on whether they have comorbidities, and if they have comorbidities, targeting them with specific drugs that are shown to have a benefit,” Pratley said.

Pratley said the studies show that newer antihyperglycemic agents can be safely used in older individuals with high CV risk or CVD.

“There may be some benefits with SGLT2 inhibitors and, perhaps, GLP-1 receptor agonists in older individuals relative to younger individuals; however, we need to better identify those older individuals that are likely at the highest risk for adverse events and might benefit most from targeted therapies,” Pratley said. – by Regina Schaffer

Reference:

Pratley RE. Diabetes and heart disease in the older patient — the evidence for targets. Presented at: Heart in Diabetes CME Conference; July 12-14, 2019; Philadelphia.

Disclosure: Pratley reports he has received grants, speaking and consultant fees paid to his institution from AstraZeneca, Boehringer Ingelheim, Eisai, Eli Lilly, GlaxoSmithKline, Glytec, Janssen, Lexicon, Ligand Pharmaceuticals, Merck, Mundipharma, Novo Nordisk, Pfizer, Sanofi and Takeda.

PHILADELPHIA — Older adults with type 2 diabetes can derive meaningful cardiovascular and renal benefits from newer antihyperglycemic agents, and data from several large CV outcomes trials suggest that treatment guidelines for this population should be redefined to reflect such findings, according to a speaker here.

Richard E. Pratley

“We need to rethink treatment guidelines for older individuals to target CVD and renal outcomes, as we are doing in the general population,” Richard E. Pratley, MD, the Samuel E. Crockett chair in diabetes research and medical director of AdventHealth Diabetes Institute, told Endocrine Today. Older individuals with type 2 diabetes have very high rates of major adverse CV events; however, they tend to derive a similar benefit [with therapy] as do younger patients. In some cases, the benefit is greater.”

Diabetes in older adults is a growing health problem, Pratley said. Approximately 11% of the world’s population is aged at least 60 years; that number will double by 2050, he said. People with diabetes are living longer, and they are vulnerable to the traditional microvascular and macrovascular complications of diabetes, as well as mortality. Diabetes among older adults is also heterogenous; some have long-standing diabetes with associated complications, whereas others are newly diagnosed with or without end-organ complications at time of presentation, Pratley said.

“The risks for these groups are quite different, and our treatment approach should be quite different as well,” Pratley said.

Historically, these older patients with type 2 diabetes were excluded from clinical trials of new drugs, despite older individuals making up a substantial fraction of patients with diabetes, Pratley said.

#
Older adults with type 2 diabetes can derive meaningful cardiovascular and renal benefits from newer antihyperglycemic agents, and data from several large CV outcomes trials suggest that treatment guidelines for this population should be redefined to reflect such findings.
Adobe Stock

“The [FDA] requirement to conduct [CV outcomes trials] has changed all that,” Pratley said. “Forty percent to 50% of patients in CV outcomes trials are aged at least 65 years. We now have much better long-term data in this population.”

New focus needed

A new Endocrine Society Clinical Practice Guideline on the treatment of older adults with diabetes, published earlier this year, recommends individualized HbA1c treatment goals based on health status. Adults who are healthy with a longer remaining life expectancy should be treated to an HbA1c goal of less than 7.5%; those with very complex or poor health and a limited remaining life expectancy should be treated to an HbA1c goal of about 8.5%.

“However, these [guidelines] are really focused on glycemic goals,” Pratley said. “As with the general population, we feel they should be individualized based on a variety of factors, including things like hypoglycemia.”

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Recent CV outcomes studies have revealed interesting data on large numbers of older adults who previously would not have been studied, Pratley said. The SAVOR-TIMI 53, EXAMINE, TECOS, CAROLINA and CARMELINA studies, which assessed DPP-IV inhibitors, included a combined 50,000 patients with type 2 diabetes, with a mean age of 61 to 66 years, he said. In SAVOR-TIMI 53, TECOS and CAROLINA, 14% of participants were aged at least 75 years. Similarly, across four CV outcomes trials assessing SGLT2 inhibitors — EMPA-REG, CANVAS, DECLARE-TIMI 58 and VERTIS-CV — the mean age of participants was 64 years. Trials for GLP-1 receptor agonists, including ELIXA, LEADER, SUSTAIN 6, EXSCEL, HARMONY, REWIND and PIONEER 6, included more than 56,000 patients with a mean age of 60 to 66 years.

“That is now thousands of patients who are elderly, who are at risk for CV disease, where we have good follow-up,” Pratley said. “This has never existed before.”

Target comorbidities

The data across these studies suggest a common theme, Pratley said: Older adults with diabetes overall did just as well on new antihyperglycemic agents as younger patients, and in some instances, they derived a greater CV or mortality benefit. In an age-stratified analysis of the LEADER trial, Pratley and colleagues observed that the HR for major adverse CV events in patients aged at least 75 years assigned liraglutide (Victoza, Novo Nordisk) was 0.7 (95% CI, 0.5-0.95) vs. 0.88 (95% CI, 0.76-1.02) in patients assigned the drug who were younger than 75 years.

“We need to redefine the targets in older individuals as we have done in the younger individuals, focusing on whether they have comorbidities, and if they have comorbidities, targeting them with specific drugs that are shown to have a benefit,” Pratley said.

Pratley said the studies show that newer antihyperglycemic agents can be safely used in older individuals with high CV risk or CVD.

“There may be some benefits with SGLT2 inhibitors and, perhaps, GLP-1 receptor agonists in older individuals relative to younger individuals; however, we need to better identify those older individuals that are likely at the highest risk for adverse events and might benefit most from targeted therapies,” Pratley said. – by Regina Schaffer

Reference:

Pratley RE. Diabetes and heart disease in the older patient — the evidence for targets. Presented at: Heart in Diabetes CME Conference; July 12-14, 2019; Philadelphia.

Disclosure: Pratley reports he has received grants, speaking and consultant fees paid to his institution from AstraZeneca, Boehringer Ingelheim, Eisai, Eli Lilly, GlaxoSmithKline, Glytec, Janssen, Lexicon, Ligand Pharmaceuticals, Merck, Mundipharma, Novo Nordisk, Pfizer, Sanofi and Takeda.

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