VIDEO: Canagliflozin’s HbA1c effect muted over time by placebo group effects

BOSTON – In a large, long-term study of canagliflozin versus placebo, an excess of discontinuations in the placebo group contributed to a dampening in the magnitude of improvement in hemoglobin A_1c.

That’s according to investigators who reported the findings at the annual meeting of the American Association of Clinical Endocrinologists.

A higher rate of starting new antihyperglycemic agents in the placebo arm also likely contributed to the decrease in the difference in HbA_1c after 52 weeks in CANVAS (Canagliflozin Cardiovascular Assessment Study), according to investigator Carol Wysham, MD, of the University of Washington, Spokane.

As previously reported, the two randomized trials in the CANVAS program showed that canagliflozin reduced risk of cardiovascular events in patients with type 2 diabetes at elevated risk of cardiovascular disease.

While the CANVAS program was not designed to assess glucose lowering – and, in fact, allowed adjustment of background antihyperglycemic agents at any time – canagliflozin patients were more likely than placebo-treated patients to achieve HbA_1c less than 7.0%.

However, the mean placebo-subtracted reduction in HbA_1c peaked at –0.64% at week 26 but shrank to –0.24% by week 338, the end of the study.

“In this case, [the analysis] is helping to understand why we might have seen a deterioration in A_1c control over a very long period of time,” Dr. Wysham explained.

 

The analysis showed that, after week 52 of the study, more patients discontinued placebo, compared with those taking canagliflozin. Over the entire CANVAS program, investigators said, the rate of discontinuation was 118.0 per 1,000 patient-years in the placebo group and 94.1 per 1,000 patient-years for canagliflozin.

In addition, while the concomitant use of antihyperglycemic agents was well balanced at baseline, the number of participants initiating new antihyperglycemic agents over the course of the study was 27% for the placebo-treated patients and 17.8% for the canagliflozin-treated patients, investigators found.

All together, the CANVAS program has provided the longest-term experience to date regarding glycemic control with canagliflozin, demonstrating greater reductions in HbA_1c, versus placebo, over about 6.5 years, Dr. Wysham and her coinvestigators said in their poster presentation.

 

The new analysis provides better clarity on why the durability in HbA_1c benefit seemed somewhat attenuated over time, according to Dr. Wysham.

“Most of us think that, if you start an SGLT2 inhibitor, especially starting it relatively early in diagnosis of diabetes, it gives you better durability than what you might see with other agents,” she said. “In fact, that’s been seen in many of the clinical trials, compared to sulphonylurea or DPP-4 inhibitor.”

Dr. Wysham reported disclosures related to AstraZeneca, Boehringer Ingelheim, Eli Lilly, Insulet, Janssen Scientific Affairs, Novo Nordisk, and Sanofi Pasteur.

SOURCE: Wysham C et al. AACE 2018, Abstract 262.

BOSTON – In a large, long-term study of canagliflozin versus placebo, an excess of discontinuations in the placebo group contributed to a dampening in the magnitude of improvement in hemoglobin A_1c.

That’s according to investigators who reported the findings at the annual meeting of the American Association of Clinical Endocrinologists.

A higher rate of starting new antihyperglycemic agents in the placebo arm also likely contributed to the decrease in the difference in HbA_1c after 52 weeks in CANVAS (Canagliflozin Cardiovascular Assessment Study), according to investigator Carol Wysham, MD, of the University of Washington, Spokane.

As previously reported, the two randomized trials in the CANVAS program showed that canagliflozin reduced risk of cardiovascular events in patients with type 2 diabetes at elevated risk of cardiovascular disease.

While the CANVAS program was not designed to assess glucose lowering – and, in fact, allowed adjustment of background antihyperglycemic agents at any time – canagliflozin patients were more likely than placebo-treated patients to achieve HbA_1c less than 7.0%.

However, the mean placebo-subtracted reduction in HbA_1c peaked at –0.64% at week 26 but shrank to –0.24% by week 338, the end of the study.

“In this case, [the analysis] is helping to understand why we might have seen a deterioration in A_1c control over a very long period of time,” Dr. Wysham explained.

 

The analysis showed that, after week 52 of the study, more patients discontinued placebo, compared with those taking canagliflozin. Over the entire CANVAS program, investigators said, the rate of discontinuation was 118.0 per 1,000 patient-years in the placebo group and 94.1 per 1,000 patient-years for canagliflozin.

In addition, while the concomitant use of antihyperglycemic agents was well balanced at baseline, the number of participants initiating new antihyperglycemic agents over the course of the study was 27% for the placebo-treated patients and 17.8% for the canagliflozin-treated patients, investigators found.

All together, the CANVAS program has provided the longest-term experience to date regarding glycemic control with canagliflozin, demonstrating greater reductions in HbA_1c, versus placebo, over about 6.5 years, Dr. Wysham and her coinvestigators said in their poster presentation.

 

The new analysis provides better clarity on why the durability in HbA_1c benefit seemed somewhat attenuated over time, according to Dr. Wysham.

“Most of us think that, if you start an SGLT2 inhibitor, especially starting it relatively early in diagnosis of diabetes, it gives you better durability than what you might see with other agents,” she said. “In fact, that’s been seen in many of the clinical trials, compared to sulphonylurea or DPP-4 inhibitor.”

Dr. Wysham reported disclosures related to AstraZeneca, Boehringer Ingelheim, Eli Lilly, Insulet, Janssen Scientific Affairs, Novo Nordisk, and Sanofi Pasteur.

SOURCE: Wysham C et al. AACE 2018, Abstract 262.

BOSTON – In a large, long-term study of canagliflozin versus placebo, an excess of discontinuations in the placebo group contributed to a dampening in the magnitude of improvement in hemoglobin A_1c.

That’s according to investigators who reported the findings at the annual meeting of the American Association of Clinical Endocrinologists.

A higher rate of starting new antihyperglycemic agents in the placebo arm also likely contributed to the decrease in the difference in HbA_1c after 52 weeks in CANVAS (Canagliflozin Cardiovascular Assessment Study), according to investigator Carol Wysham, MD, of the University of Washington, Spokane.

As previously reported, the two randomized trials in the CANVAS program showed that canagliflozin reduced risk of cardiovascular events in patients with type 2 diabetes at elevated risk of cardiovascular disease.

While the CANVAS program was not designed to assess glucose lowering – and, in fact, allowed adjustment of background antihyperglycemic agents at any time – canagliflozin patients were more likely than placebo-treated patients to achieve HbA_1c less than 7.0%.

However, the mean placebo-subtracted reduction in HbA_1c peaked at –0.64% at week 26 but shrank to –0.24% by week 338, the end of the study.

“In this case, [the analysis] is helping to understand why we might have seen a deterioration in A_1c control over a very long period of time,” Dr. Wysham explained.

 

The analysis showed that, after week 52 of the study, more patients discontinued placebo, compared with those taking canagliflozin. Over the entire CANVAS program, investigators said, the rate of discontinuation was 118.0 per 1,000 patient-years in the placebo group and 94.1 per 1,000 patient-years for canagliflozin.

In addition, while the concomitant use of antihyperglycemic agents was well balanced at baseline, the number of participants initiating new antihyperglycemic agents over the course of the study was 27% for the placebo-treated patients and 17.8% for the canagliflozin-treated patients, investigators found.

All together, the CANVAS program has provided the longest-term experience to date regarding glycemic control with canagliflozin, demonstrating greater reductions in HbA_1c, versus placebo, over about 6.5 years, Dr. Wysham and her coinvestigators said in their poster presentation.

 

The new analysis provides better clarity on why the durability in HbA_1c benefit seemed somewhat attenuated over time, according to Dr. Wysham.

“Most of us think that, if you start an SGLT2 inhibitor, especially starting it relatively early in diagnosis of diabetes, it gives you better durability than what you might see with other agents,” she said. “In fact, that’s been seen in many of the clinical trials, compared to sulphonylurea or DPP-4 inhibitor.”

Dr. Wysham reported disclosures related to AstraZeneca, Boehringer Ingelheim, Eli Lilly, Insulet, Janssen Scientific Affairs, Novo Nordisk, and Sanofi Pasteur.

SOURCE: Wysham C et al. AACE 2018, Abstract 262.