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▎Editor of WuXi AppTec's content team In the coming decades, the dual prevalence of type 2 diabetes (T2DM) and obesity will continue to be a major global health challenge
.
For patients with T2DM and obesity, because life>
.
Recently, "Nature Reviews Endocrinology" (Nature Reviews Endocrinology) published an annual review of the field of T2DM treatment in 2021, in-depth introduction to the latest clinical research progress in the prevention and treatment of T2DM and obesity, and "incretin" as the field Significant progress brought about
.
These key breakthroughs include: The STEP-3 test confirmed that the GLP1 receptor agonist smeglutide (once a week) showed considerable safety and effectiveness in the treatment of obesity, and the average weight of all subjects was reduced Up to 15%; SURPASS-1 study shows that Tirzepatide (GIP and GLP-1 receptor dual agonist) can reduce the HbA1c level of T2DM patients by up to 2%, and can bring a dose-dependent weight loss (7 kg to 9 kg ); The SURPASS-2 study (head-to-head study) confirmed that Tirzepatide showed unique advantages in reducing HbA1c levels and body weight.
At the same time, the incidence of gastrointestinal adverse reactions in patients was similar; the SURPASS-3 study (head-to-head study) confirmed Tirzepatide has a unique advantage over insulin degludec in reducing HbA1c levels and body weight.
At the same time, patients have a lower risk of hypoglycemia
.
Screenshot source: Nature Reviews Endocrinology T2DM meets the "double nemesis", weight loss + hypoglycemic "two-pronged" incretin, including glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), stable in blood sugar It plays an important role in state and energy balance
.
GLP1 receptor agonists (GLP1RAs) can bring benefits such as lowering blood sugar, reducing weight, and reducing the risk of cardiovascular events.
At present, there is sufficient evidence-based evidence for the treatment of T2DM
.
GIP can also promote glucose-dependent insulin secretion, and may mediate a greater degree of secretin effect than GLP1
.
It is worth noting that both GLP1 and GIP can inhibit the level of glucagon in the human body under hyperglycemia, and GIP also has the effect of promoting glucagon in hypoglycemia and normal blood sugar
.
For healthy individuals and T2DM patients, the combined administration of GLP1 and GIP has a synergistic insulinotropic effect
.
In recent years, incretin has attracted much attention as a new type of hypoglycemic agent
.
Evidence from a large randomized controlled study showed that under the secretin-based treatment regimen, HbA1c levels and body weight of T2DM patients were reduced to a considerable degree at the same time
.
Based on these findings, incretin is expected to change the pattern of diabetes treatment
.
Secretin 2021 important research summary GLP1 receptor agonist smegliutide: reduce body weight by 15% 2021, GLP1 receptor agonist smeglutide for the treatment of obesity Phase III trial (STEP-3 study) results Published
.
This is a global, double-blind, randomized, placebo-controlled trial involving 1961 subjects
.
The inclusion criteria of subjects were: not suffering from T2DM; BMI ≥ 30 kg/m², or BMI ≥ 27 kg/m² but accompanied by at least one weight-related symptom
.
The subjects were randomly assigned in a 2:1 ratio to receive 68 weeks of smeglutide (2.
4 mg, once a week) or placebo treatment, plus life>
.
The results of the study showed that compared with the placebo group, the weight of the patients in the smeglutide group was reduced by 14.
9% and 2.
4%, respectively
.
In addition, 86% of patients in the smeglutide group had a weight loss of ≥5%, while the proportion of patients in the placebo group was only 31.
5%
.
This study confirmed the effectiveness and safety of the GLP1 receptor agonist smegaglutide for obesity management
.
GIP and GLP-1 receptor dual agonist Tirzepatide: 2% lower blood sugar, 7 kg-9 kg weight loss GIP and GLP-1 receptor dual agonists have unique advantages in inducing dose-dependent weight loss, lowering blood sugar, and reducing food intake
.
Tirzepatide is a dual agonist of GIP and GLP-1 receptors, and is the first "dual" incretin to carry out a global phase III trial
.
In its Phase I and Phase II studies, Tirzepatide (with a weekly dose range of up to 15 mg) can reduce HbA1c levels in patients with T2DM by up to 2.
4% and weight loss by up to 11.
3 kg
.
In addition, the SURPASS clinical project has also reported the efficacy data of Tirzepatide
.
SURPASS-1 is a 40-week double-blind, placebo-controlled trial to evaluate the effect of Tirzepatide monotherapy.
The study included 478 subjects from 52 medical centers.
.
The subjects were randomized to receive placebo or Tirzepatide (dose of 5 mg, 10 mg or 15 mg, once a week) at a ratio of 1:1:1
.
The results of the study showed that compared with patients in the placebo group, more patients treated with Tirzepatide reached the target of HbA1c<7.
0% (20% vs 87%~92%)
.
Tirzepatide can produce a dose-dependent weight loss of 7.
0 kg to 9.
5 kg
.
Tirzepatide vs.
GLP1 receptor agonist SURPASS-2 is a head-to-head comparison study designed to evaluate the difference in efficacy between Tirzepatide and GLP1 receptor agonist smeglutide in patients with T2DM
.
The study included 1879 patients with T2DM with poor blood glucose control treated with metformin (baseline HbA1c 7%~10% and BMI≥25 kg/m²)
.
Patients were randomly assigned to receive Tirzepatide (5 mg, 10 mg, or 15 mg, once a week) or smeglutide (1 mg, once a week) treatment for 40 weeks
.
The results of the study showed that at week 40, the average HbA1c of patients treated with 5 mg, 10 mg, and 15 mg Tirzepatide decreased by 2.
01%, 2.
24%, and 2.
3%, respectively, while those treated with smeglutide decreased 1.
86%
.
There are statistically significant differences between the two groups, and the results of the study support Tirzepatide treatment
.
In addition, patients treated with 5 mg, 10 mg, and 15 mg Tirzepatide showed a dose-dependent decrease in body weight by 7.
6 kg, 9.
3 kg, and 11.
2 kg, respectively; while patients who received simegliutide treatment decreased by 5.
7 kg (P<0.
001)
.
There is also a statistically significant difference between smeglutide and the lowest dose of Tirzepatide in reducing the weight of patients
.
65%~80% of the patients in the Tirzepatide group and 54% of the patients in the smeglutide group lost at least 5% of their body weight.
At the same time, the incidence of gastrointestinal adverse reactions was similar
.
Tirzepatide vs.
insulin degludec SURPASS-3 is a randomized, open-label clinical trial
.
A total of 1444 patients were enrolled in the study, and the enrolled patients were treated with Tirzepatide (5 mg, 10 mg, or 15 mg, once a week) or insulin degludec (once a day)
.
The study included patients who received metformin or metformin combined with SGLT-2 inhibitors for poor blood glucose control (baseline HbA1c 8.
17%)
.
The results of the study showed that in the 52nd week of treatment, patients treated with 5 mg, 10 mg, and 15 mg Tirzepatide had a reduction in HbA1c by 1.
93%, 2.
20%, and 2.
37%, respectively, while those receiving deglubber were 1.
34% (P<0.
0001 for all doses of Tirzepatide treatment)
.
Compared with placebo, patients in the Tirzepatide group lost more weight, but at the same time the incidence of gastrointestinal adverse reactions was also higher
.
1%~2% of patients in the Tirzepatide group had severe hypoglycemia or a blood sugar level of <3 mmol/L, compared with 7% in the insulin degludec group
.
Summary In general, GIP and GLP-1 receptor dual agonists compared to GLP1 receptor agonists showed unique advantages in reducing HbA1c and body weight, and the gastrointestinal tolerance of the two was similar, and treatment was stopped due to adverse events The possibilities are low
.
It is worth noting that the current research data for patients of different ethnicities is still relatively limited
.
We know that Asian people can suffer from T2DM at a lower level of BMI.
The role of "dual" incretin in this group of people still needs to be further studied in the future.
In the future, we will also need to pass longer follow-up and phase IV studies.
To identify more safety signals
.
The review finally pointed out that in the future, we need to better position the different therapeutic status of GIP and GLP-1 receptor agonists and GLP1 receptor agonists in the treatment of T2DM, based on different genetic, environmental and clinical factors of patients.
Choose
.
Related reading "The Lancet" sub-issue: Dapagliflozin reduces new-onset diabetes by 33%, and two key studies add more evidence of benefit! ADA's latest diabetes guidelines: It is recommended that everyone start screening at the age of 35.
Metformin may not be the "first choice".
.
.
1 person dies of diabetes every 5 seconds, and a quarter of the patients are in China! The latest Global Diabetes Map released a substantial increase in "non-traditional" concurrent diseases of diabetic patients! The 16-year data of the "Lancet" sub-journal reveals the reference material for the changes in the etiology of hospitalization[1] Chow, E.
, Chan, JCN The emerging role of incretins and twincretins.
Nat Rev Endocrinol (2021).
https://doi.
org/ 10.
1038/s41574-021-00607-w Disclaimer: WuXi AppTec's content team focuses on introducing global biomedical health research progress
.
This article is for the purpose of information exchange only.
The opinions expressed in the article do not represent the position of WuXi AppTec, nor does it mean that WuXi AppTec supports or opposes the views in the article
.
This article is not a treatment recommendation either
.
If you need guidance on the treatment plan, please go to a regular hospital for treatment
.
.
For patients with T2DM and obesity, because life>
.
Recently, "Nature Reviews Endocrinology" (Nature Reviews Endocrinology) published an annual review of the field of T2DM treatment in 2021, in-depth introduction to the latest clinical research progress in the prevention and treatment of T2DM and obesity, and "incretin" as the field Significant progress brought about
.
These key breakthroughs include: The STEP-3 test confirmed that the GLP1 receptor agonist smeglutide (once a week) showed considerable safety and effectiveness in the treatment of obesity, and the average weight of all subjects was reduced Up to 15%; SURPASS-1 study shows that Tirzepatide (GIP and GLP-1 receptor dual agonist) can reduce the HbA1c level of T2DM patients by up to 2%, and can bring a dose-dependent weight loss (7 kg to 9 kg ); The SURPASS-2 study (head-to-head study) confirmed that Tirzepatide showed unique advantages in reducing HbA1c levels and body weight.
At the same time, the incidence of gastrointestinal adverse reactions in patients was similar; the SURPASS-3 study (head-to-head study) confirmed Tirzepatide has a unique advantage over insulin degludec in reducing HbA1c levels and body weight.
At the same time, patients have a lower risk of hypoglycemia
.
Screenshot source: Nature Reviews Endocrinology T2DM meets the "double nemesis", weight loss + hypoglycemic "two-pronged" incretin, including glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), stable in blood sugar It plays an important role in state and energy balance
.
GLP1 receptor agonists (GLP1RAs) can bring benefits such as lowering blood sugar, reducing weight, and reducing the risk of cardiovascular events.
At present, there is sufficient evidence-based evidence for the treatment of T2DM
.
GIP can also promote glucose-dependent insulin secretion, and may mediate a greater degree of secretin effect than GLP1
.
It is worth noting that both GLP1 and GIP can inhibit the level of glucagon in the human body under hyperglycemia, and GIP also has the effect of promoting glucagon in hypoglycemia and normal blood sugar
.
For healthy individuals and T2DM patients, the combined administration of GLP1 and GIP has a synergistic insulinotropic effect
.
In recent years, incretin has attracted much attention as a new type of hypoglycemic agent
.
Evidence from a large randomized controlled study showed that under the secretin-based treatment regimen, HbA1c levels and body weight of T2DM patients were reduced to a considerable degree at the same time
.
Based on these findings, incretin is expected to change the pattern of diabetes treatment
.
Secretin 2021 important research summary GLP1 receptor agonist smegliutide: reduce body weight by 15% 2021, GLP1 receptor agonist smeglutide for the treatment of obesity Phase III trial (STEP-3 study) results Published
.
This is a global, double-blind, randomized, placebo-controlled trial involving 1961 subjects
.
The inclusion criteria of subjects were: not suffering from T2DM; BMI ≥ 30 kg/m², or BMI ≥ 27 kg/m² but accompanied by at least one weight-related symptom
.
The subjects were randomly assigned in a 2:1 ratio to receive 68 weeks of smeglutide (2.
4 mg, once a week) or placebo treatment, plus life>
.
The results of the study showed that compared with the placebo group, the weight of the patients in the smeglutide group was reduced by 14.
9% and 2.
4%, respectively
.
In addition, 86% of patients in the smeglutide group had a weight loss of ≥5%, while the proportion of patients in the placebo group was only 31.
5%
.
This study confirmed the effectiveness and safety of the GLP1 receptor agonist smegaglutide for obesity management
.
GIP and GLP-1 receptor dual agonist Tirzepatide: 2% lower blood sugar, 7 kg-9 kg weight loss GIP and GLP-1 receptor dual agonists have unique advantages in inducing dose-dependent weight loss, lowering blood sugar, and reducing food intake
.
Tirzepatide is a dual agonist of GIP and GLP-1 receptors, and is the first "dual" incretin to carry out a global phase III trial
.
In its Phase I and Phase II studies, Tirzepatide (with a weekly dose range of up to 15 mg) can reduce HbA1c levels in patients with T2DM by up to 2.
4% and weight loss by up to 11.
3 kg
.
In addition, the SURPASS clinical project has also reported the efficacy data of Tirzepatide
.
SURPASS-1 is a 40-week double-blind, placebo-controlled trial to evaluate the effect of Tirzepatide monotherapy.
The study included 478 subjects from 52 medical centers.
.
The subjects were randomized to receive placebo or Tirzepatide (dose of 5 mg, 10 mg or 15 mg, once a week) at a ratio of 1:1:1
.
The results of the study showed that compared with patients in the placebo group, more patients treated with Tirzepatide reached the target of HbA1c<7.
0% (20% vs 87%~92%)
.
Tirzepatide can produce a dose-dependent weight loss of 7.
0 kg to 9.
5 kg
.
Tirzepatide vs.
GLP1 receptor agonist SURPASS-2 is a head-to-head comparison study designed to evaluate the difference in efficacy between Tirzepatide and GLP1 receptor agonist smeglutide in patients with T2DM
.
The study included 1879 patients with T2DM with poor blood glucose control treated with metformin (baseline HbA1c 7%~10% and BMI≥25 kg/m²)
.
Patients were randomly assigned to receive Tirzepatide (5 mg, 10 mg, or 15 mg, once a week) or smeglutide (1 mg, once a week) treatment for 40 weeks
.
The results of the study showed that at week 40, the average HbA1c of patients treated with 5 mg, 10 mg, and 15 mg Tirzepatide decreased by 2.
01%, 2.
24%, and 2.
3%, respectively, while those treated with smeglutide decreased 1.
86%
.
There are statistically significant differences between the two groups, and the results of the study support Tirzepatide treatment
.
In addition, patients treated with 5 mg, 10 mg, and 15 mg Tirzepatide showed a dose-dependent decrease in body weight by 7.
6 kg, 9.
3 kg, and 11.
2 kg, respectively; while patients who received simegliutide treatment decreased by 5.
7 kg (P<0.
001)
.
There is also a statistically significant difference between smeglutide and the lowest dose of Tirzepatide in reducing the weight of patients
.
65%~80% of the patients in the Tirzepatide group and 54% of the patients in the smeglutide group lost at least 5% of their body weight.
At the same time, the incidence of gastrointestinal adverse reactions was similar
.
Tirzepatide vs.
insulin degludec SURPASS-3 is a randomized, open-label clinical trial
.
A total of 1444 patients were enrolled in the study, and the enrolled patients were treated with Tirzepatide (5 mg, 10 mg, or 15 mg, once a week) or insulin degludec (once a day)
.
The study included patients who received metformin or metformin combined with SGLT-2 inhibitors for poor blood glucose control (baseline HbA1c 8.
17%)
.
The results of the study showed that in the 52nd week of treatment, patients treated with 5 mg, 10 mg, and 15 mg Tirzepatide had a reduction in HbA1c by 1.
93%, 2.
20%, and 2.
37%, respectively, while those receiving deglubber were 1.
34% (P<0.
0001 for all doses of Tirzepatide treatment)
.
Compared with placebo, patients in the Tirzepatide group lost more weight, but at the same time the incidence of gastrointestinal adverse reactions was also higher
.
1%~2% of patients in the Tirzepatide group had severe hypoglycemia or a blood sugar level of <3 mmol/L, compared with 7% in the insulin degludec group
.
Summary In general, GIP and GLP-1 receptor dual agonists compared to GLP1 receptor agonists showed unique advantages in reducing HbA1c and body weight, and the gastrointestinal tolerance of the two was similar, and treatment was stopped due to adverse events The possibilities are low
.
It is worth noting that the current research data for patients of different ethnicities is still relatively limited
.
We know that Asian people can suffer from T2DM at a lower level of BMI.
The role of "dual" incretin in this group of people still needs to be further studied in the future.
In the future, we will also need to pass longer follow-up and phase IV studies.
To identify more safety signals
.
The review finally pointed out that in the future, we need to better position the different therapeutic status of GIP and GLP-1 receptor agonists and GLP1 receptor agonists in the treatment of T2DM, based on different genetic, environmental and clinical factors of patients.
Choose
.
Related reading "The Lancet" sub-issue: Dapagliflozin reduces new-onset diabetes by 33%, and two key studies add more evidence of benefit! ADA's latest diabetes guidelines: It is recommended that everyone start screening at the age of 35.
Metformin may not be the "first choice".
.
.
1 person dies of diabetes every 5 seconds, and a quarter of the patients are in China! The latest Global Diabetes Map released a substantial increase in "non-traditional" concurrent diseases of diabetic patients! The 16-year data of the "Lancet" sub-journal reveals the reference material for the changes in the etiology of hospitalization[1] Chow, E.
, Chan, JCN The emerging role of incretins and twincretins.
Nat Rev Endocrinol (2021).
https://doi.
org/ 10.
1038/s41574-021-00607-w Disclaimer: WuXi AppTec's content team focuses on introducing global biomedical health research progress
.
This article is for the purpose of information exchange only.
The opinions expressed in the article do not represent the position of WuXi AppTec, nor does it mean that WuXi AppTec supports or opposes the views in the article
.
This article is not a treatment recommendation either
.
If you need guidance on the treatment plan, please go to a regular hospital for treatment
.
