DOM: Long-term effects of dapagliflozin combined with saxagliptin and glimepiride on type 2 diabetes patients treated with metformin as background

Although there are many hypoglycemic drugs, the progress of type 2 diabetes (T2D) makes it difficult to maintain blood sugar control
.

Metformin (MET) is the first choice of initial drug treatment.

Metformin (MET) is the first choice of initial drug treatment.

Methods: The expansion was a 52-week global, multi-center, parallel-group controlled, double-blind study (NCT02419612)
.

Eligible participants enter the 2-week screening and 2-week testing phase

²

The MRI sub-study included all participants in the study.
They had a BMI of 20.
0-40.
0 kg/m2 at the time of enrollment, and a maximum weight of 140 kg to accommodate MRI scans.
There were no other contraindications for MRI scans
.

Participants assigned to the MRI sub-study had the imaging site scanned within 2 weeks before the follow-up, within ±2 weeks after the 52-week visit, and within ±4 weeks after the 122-week visit

The secondary endpoints of the entire 156-week study were: the time of intensive treatment during the 156-week treatment period, and the proportion of participants who achieved therapeutic blood glucose relief at 156 weeks
.

All other goals are exploratory, including glycosylated hemoglobin (HbA1c), fasting blood glucose (FPG), systolic blood pressure (SBP), total body weight, and serum alanine aminotransferase (ALT) and serum alanine aminotransferase (ALT) of all participants evaluated at week 156.

In the MRI substudy, the endpoints included the average change in liver fat percentage, SAT, and VAT volume from baseline at 52 and 122 weeks
.

This substudy evaluated the average changes in HbA1c, serum ALT and AST levels, body weight, and fibrosis-4 (FIB-4) scores from baseline during the 156-week treatment period

Results: A total of 382 participants, 338 participants completed the 104-week extended follow-up (MRI sub-study, n=82)
.

During 156 weeks, the intensive treatment requirement of DAPA+SAXA+MET (37.

DAPA+SAXA+MET demand for intensive treatment (37.

Figure 1 Time from 156 weeks of treatment to intensive treatment, Kaplan-Meier chart (random analysis set)
.

Intensive treatment is defined as: adding insulin or other hypoglycemic drugs to rescue treatment, or stopping treatment due to poor blood sugar control

Figure 1 Time from 156 weeks of treatment to intensive treatment, Kaplan-Meier chart (random analysis set)
.
Intensive treatment is defined as: adding insulin or other hypoglycemic drugs to rescue treatment, or stopping treatment due to poor blood sugar control
.
If treatment enhancement has not occurred at 156 weeks, the time of treatment enhancement is reviewed
.
Participants rescued in week 156 were counted as having incidents for analysis
.
"J" and "0" represent the observation results after review
.
DAPA, dapagliflozin; GLIM, glimepiride; MET, metformin; N, the number of participants in the treatment group; r, the number of risk participants at this time point; SAXA, saxagliptin

Figure 2 The adjusted average change of glycosylated hemoglobin (HbA1c) 156 weeks before the rescue and treatment stop (random analysis set)
.
Repeated measures analysis, least squares mean (95% confidence interval [CI])
.
Participants with or without missing baseline assessment and ≥1 post-baseline assessment were included in the analysis
.
(DAPA+Saxa+MET, 218; Glim+MET, 212)
.
Week 0 refers to the baseline value
.
The baseline is defined as the participants in the random analysis set, including no-missing baseline assessment and ≥1 post-baseline assessment
.
DAPA, dapagliflozin; GLIM, glimepiride; MET, metformin; N, the number of participants in the treatment group; r, the number of risk participants at this point in time; SAXA, saxagliptin

Figure 2 The adjusted average change of glycosylated hemoglobin (HbA1c) 156 weeks before the rescue and treatment stop (random analysis set)
.
Repeated measures analysis, least squares mean (95% confidence interval [CI])
.
Participants with or without missing baseline assessment and ≥1 post-baseline assessment were included in the analysis
.
(DAPA+Saxa+MET, 218; Glim+MET, 212)
.
Week 0 refers to the baseline value
.
The baseline is defined as the participants in the random analysis set, including no-missing baseline assessment and ≥1 post-baseline assessment
.
DAPA, dapagliflozin; GLIM, glimepiride; MET, metformin; N, the number of participants in the treatment group; r, the number of risk participants at this point in time; SAXA, saxagliptin

Table 156 Selected AEs during the 156-week treatment period (treatment participant data set)

Table 156 Selected AEs during the 156-week treatment period (treatment participant data set)

Figure 3 (A) liver fat (proton density fat fraction [PDFF]), (B) visceral adipose tissue (VAT) volume, (C) subcutaneous adipose tissue (SAT) volume, and (D) total body weight at 52 weeks and The 156-week adjusted mean weight change from baseline (random analysis set of the magnetic resonance imaging sub-study) adjusted mean change
.
Before rescue and treatment stop, 52 weeks (except for analysis of covariance [ANCOVA], mixed model of total repeated measures [MMRM]) and the least square difference of 122 or 156 (MMRM) plus glimepiride (GLIM) The P value of metformin (MET) is adjusted to the baseline value
.
In the dapagliflozin (DAPA) + saxaliptin (SAXA) + MET group, the average liver fat, VAT, and SAT volume at 122 weeks were reduced by 32%, 10%, and 9%, respectively, compared with baseline
.
The relative reduction is calculated based on the baseline and the unadjusted average at week 122
.
MMRM includes the baseline value of this variable and patients with a post-value ≥1
.
The analysis of variance included patients with baseline and week 52 results
.
Δ, the least squares mean difference from GLIM+MET; CI, confidence interval; n, the number of patients included in the analysis

Figure 3 (A) liver fat (proton density fat fraction [PDFF]), (B) visceral adipose tissue (VAT) volume, (C) subcutaneous adipose tissue (SAT) volume, and (D) total body weight at 52 weeks and The 156-week adjusted mean weight change from baseline (random analysis set of the magnetic resonance imaging sub-study) adjusted mean change
.
Before rescue and treatment stop, 52 weeks (except for analysis of covariance [ANCOVA], mixed model of total repeated measures [MMRM]) and the least square difference of 122 or 156 (MMRM) plus glimepiride (GLIM) The P value of metformin (MET) is adjusted to the baseline value
.
In the dapagliflozin (DAPA) + saxaliptin (SAXA) + MET group, the average liver fat, VAT, and SAT volume at 122 weeks were reduced by 32%, 10%, and 9%, respectively, compared with baseline
.
The relative reduction is calculated based on the baseline and the unadjusted average at week 122
.
MMRM includes the baseline value of this variable and patients with a post-value ≥1
.
The analysis of variance included patients with baseline and week 52 results
.
Δ, the least squares mean difference from GLIM+MET; CI, confidence interval; n, the number of patients included in the analysis

Conclusion: In general, in T2D, DAPA+SAXA+MET can control blood sugar better than GLIM+MET, bringing more metabolic benefits and therapeutic effects
.

In general, in T2D, DAPA+SAXA+MET can better control blood sugar than GLIM+MET, and bring more metabolic benefits and therapeutic effects
.

Original source:

Frías JP, Maaske J, Suchower L,et al.
Long-term effects of dapagliflozin plus saxagliptin versus glimepiride on a background of metformin in patients with type 2 diabetes: results of a 104-week extension to a 52-week randomised, phase 3 study and liver fat MRI sub-study.
Diabetes Obes Metab 2021 Sep 13

Long-term effects of dapagliflozin plus saxagliptin versus glimepiride on a background of metformin in patients with type 2 diabetes: results of a 104-week extension to a 52-week randomised, phase 3 study and liver fat MRI sub-study.
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