Treatment Intensification with Injectable Therapies Beyond GLP-1 RA Based Therapy in T2DM Guideline

Questionnaire Deadline：12.00 pm August 27, 2025, Beijing time
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1. Switched to another GLP-1 vs. Unchanged GLP-1

① How substantial are the desirable anticipated effects?

Desirable effects

1)Critical outcome

① HbA1c change value (%) at 12 weeks: There is a trivial effect in reducing the HbA1c change.（RCT=1, N=31，MD 0.05 lower (0.44 lower to 0.34 higher)，very low-certainty evidence）

② HbA1c change value (%) at 24 weeks: There is a small effect in reducing the HbA1c change. (RCT=1, N=39，MD 0.5 lower (0.94 lower to 0.06 lower), very low-certainty evidence)

2)Important outcome

① FPG change value (mmol/L) at 12 weeks: There is a large effect in reducing the FPG change value. (RCT=1, N=31, MD 28.5 lower (40.08 lower to 16.92 lower), very low-certainty evidence))

② Diabetes Treatment Satisfaction Questionnaire (DTSQ)-Frequency of hyperglycemia and hypoglycemia score (measuring range：0-6 points，lower is better) at 12 weeks:（RCT=1, N=31，MD 0.6 lower(1.83 lower to 0.63 higher), very low-certainty evidence).

③ Diabetes Treatment-Related Quality of Life Questionnaire (DTR-QOL)-total score (measuring range: 0-100 points higher is better) at 12 weeks: (RCT=1, N=31, MD 12.6 higher (4.42 higher to 20.78 higher), very low-certainty evidence))

④ Time in range (%) at 24 weeks: (RCT=1, N=39, MD 15.9 higher (4.87 higher to 26.93 higher), very low-certainty evidence))

⑤ Body weight change value (%, change value/baseline value) at 24 weeks：There is a trivial effect in reducing the body weight. (RCT=1, N=39, MD 0.47 lower (14.81 lower to 13.87 higher), very low-certainty evidence))

⑥ FPG change value (mmol/L) at 24 weeks: There is a trivial effect in reducing the FPG. (RCT=1, N=39, MD 0.04 mmol/L lower (0.95 lower to 0.87 higher), very low-certainty evidence))

⑦ DTSQ-Frequency of hyperglycemia and hypoglycemia(measuring range：0-6 points，lower is better) at 24 weeks: (RCT=1, N=39, MD 1.7 fewer (3.14 fewer to 0.26 fewer), very low-certainty evidence))

⑧ Eating behavior total score (measuring range: 0-220 points lower is better) at 24 weeks: (RCT=1, N=39, MD 2.6 lower (13.68 lower to 8.48 higher), very low-certainty evidence))

Other comments

② How substantial are the undesirable anticipated effects?

Undesirable effects

1)Important outcome

① Body weight change value (%, change value/baseline value) at 12 weeks: There is a trivial effect in reducing the body weight. (RCT=1, N=31，MD 1.33 higher (37.27 lower to 39.93 higher), very low-certainty evidence)

② DTSQ-total score (measuring range：0-36 points higher is better) at 12 weeks:  (RCT=1, N=31, MD 4.8 lower (8.3 lower to 1.3 lower), very low-certainty evidence)

③ Time below range (%) at 24 weeks：(RCT=1, N=39, MD 0.2 higher (1.44 lower to 1.84 higher), very low-certainty evidence)

④ DTSQ-total score (measuring range: 0-36 points higher is better) at 24 weeks: (RCT=1, N=39, MD 4.4 lower (9.3 lower to 0.5 higher), very low-certainty evidence)

Other comments

③ Is there important uncertainty about or variability in how much people value the main outcomes?

After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.

Other comments
④ Does the balance between desirable and undesirable effects favor the intervention or the comparison?
Other comments

⑤ Resources required

After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.

Other comments

⑥ What is the certainty of the evidence of resource requirements?

After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.
Other comments

⑦ Does the cost-effectiveness of the intervention favor the intervention or the comparison?

After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.
Other comments

⑧ What would be the impact on health equity?

After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.
Other comments

⑨ Is the intervention acceptable to key interest-holders?

After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.
Other comments

⑩ Is the intervention feasible to implement?

After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.
Other comments

⑪ Type of recommendation?

Other comments

2. Switched to FRC vs. Unchanged GLP-1

① How substantial are the desirable anticipated effects?

Desirable effects

1)Critical outcome

①HbA1c change value (%) at 26 weeks: There is a small effect in reducing the HbA1c change.(RCT=2, N=943, MD 0.8 lower (1.19 lower to 0.4 lower), low-certainty evidence)

②HbA1c control <7% at 26 weeks: There is a large effect in proportion of patients achieving HbA1c control <7%.(RCT=2, N=943, 361 more per 1,000 (262 more to 477 more), moderate-certainty evidence)

③HbA1c control <6.5% at 26 weeks:There is a large effect in proportion of patients achieving HbA1c control <6.5%. (RCT=2, N=943,334 more per 1,000 (173 more to 575 more), moderate-certainty evidence)

④Safety control at 26 weeks:There is a large effect in proportion of patients achieving safety control both Safety control without ≤ 54 mg/d(RCT=1, N=505, 314 more per 1,000 (195 more to 465 more), Low)and ≤ 70mg/dL(RCT=1, N=505,180 more per 1,000 (83 more to 306 more), low-certainty evidence)).

2)Important outcome

①FPG change value (mmol/L) at 26 weeks: There is a large effect in reducing the FPG. (RCT=2, N=943, MD 1.87 lower (2.83 lower to 0.91 lower), very low-certainty evidence)

②DTSQ-total score (measuring range: 0-36 points higher is better) at 26 weeks: (RCT=1, N=438, MD 2 higher (1.1 higher to 2.9 higher), very low-certainty evidence)

③TRIM-D-total score(measuring range: 0-100 points higher is better): (RCT=1, N=438, MD 5 higher (2.9 higher to 7.2 higher), very low-certainty evidence)

Other comments
② How substantial are the undesirable anticipated effects?
Undesirable effects

1)Critical outcome

① Incidence of hypolycemia at 26 weeks: There is a large effect in increasing the incidence of hypoglycemia. (RCT=1, N=511,255 more per 1,000 (100 more to 606 more), low-certainty evidence).

Another study Linjawi 2017 reportedIncidence of hypolycemia as (I: 2.82-episodes per PYE, C: 0.12-episodes per PYE,  estimated rate ratio (ERR) of 25.36 (10.6; 60.5) 95%CI).

② Incidence of severe hypoglycemia at 26 weeks:There is a moderate effect in increasing the incidence of severe hypoglycemia. (RCT=2, N=949,17 more per 1,000 (1 fewer to 304 more), low-certainty evidence)

2)Important outcome

① Body weight change value (%, change value/baseline value) at 26 weeks: There is a moderate effect in reducing the body weight. (RCT=2, N=943,MD 3.33 higher (2.61 higher to 4.04 higher), low-certainty evidence)

② Gastrointestinal disorders at 26 weeks: There is a moderate effect in reducing the body weight.(RCT=1, N=511,114 more per 1,000 (39 more to 231 more), low-certainty evidence)

Other comments
③ Is there important uncertainty about or variability in how much people value the main outcomes?
After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.
Other comments
④ Does the balance between desirable and undesirable effects favor the intervention or the comparison?
Other comments
⑤ Resources required
After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.
Other comments

⑥ What is the certainty of the evidence of resource requirements?

After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.
Other comments

⑦ Does the cost-effectiveness of the intervention favor the intervention or the comparison?

After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.
Other comments

⑧ What would be the impact on health equity?

After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.
Other comments

⑨ Is the intervention acceptable to key interest-holders?

After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.
Other comments

⑩ Is the intervention feasible to implement?

After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.
Other comments

⑪ Type of recommendation?

Other comments

3. Add basal insulin vs. Unchanged GLP-1 

① How substantial are the desirable anticipated effects?

Desirable effects

1)Critical outcome

① HbA1c change value (%) at 26 weeks: There is a small effect in reducing the HbA1c change. (RCT=2, N=665,MD 0.7 lower (1.05 lower to 0.34 lower), low-certainty evidence)

② HbA1c control <7% at 26 weeks: There is a large effect in proportion of patients achieving HbA1c control <7%. (RCT=2, N=665,334 more per 1,000 (230 more to 460 more),  moderate-certainty evidence)

③ HbA1c control<6.5% at 26 weeks: There is a large effect in proportion of patients achieving HbA1c control <6.5%. (RCT=1, N=319,122 more per 1,000 (30 more to 308 more), low -certainty evidence)

④ Safety control- at 26 weeks: There is large effect in proportion of patients achieving safety control. (RCT=1, N=319,120 more per 1,000 (28 more to 286 more), low-certainty evidence)

⑤ Incidence of severe hypoglycemia at 26 weeks: No severe hypoglycemia occurred in both group. (RCT=2, N=668,0 fewer per 1,000 (0 fewer to 0 fewer), low-certainty evidence)

⑥ HbA1c (%) at 52 weeks: There is a small effect in reducing the HbA1c change. (RCT=1, N=323,MD 0.51 lower (0.76 lower to 0.26 lower), very low-certainty evidence)

⑦ HbA1c control ＜7% at 52 weeks: There is a large effect in proportion of patients achieving HbA1c control <7%. (RCT=1, N=319,296 more per 1,000 (152 more to 497 more), low-certainty evidence)

⑧ HbA1c control ＜6.5% at 52 weeks: There is a large effect in proportion of patients achieving HbA1c control < 6.5%. (RCT=1, N=319, 152 more per 1,000(47 more to 351 more), very low-certainty evidence )

⑨ Safety control at 52 weeks: There is a large effect in proportion of patients achieving safety control.(RCT=1, N=319,88 more per 1,000 (3 fewer to 227 more), very low-certainty evidence)

2)Important outcome

① Body weight change value (%, change value/baseline value) at 26 weeks: There is a trivial effect in reducing the body weight. (RCT=1, N=319, MD 0.95 lower (2.1 lower to 0.2 higher), low-certainty evidence)

② Gastrointestinal disorders-Nause at 26 weeks: There is a trivial effect in Gastrointestinal disorders-Nausea. (RCT=2, N=668, 4 fewer per 1,000 (25 fewer to 40 more), low-certainty evidence)

③ FPG change value (mmol/L) at 26 weeks: There is a large effect in reducing the FPG. (RCT=2, N=665, MD 2.12 lower (2.95 lower to 1.29 lower), very low-certainty evidence)

④ Postprandial blood glucose-breakfast at 52 weeks: There is a large effect in reducing postprandial blood glucose. (RCT=1, N=323,MD 1.74 lower (2.32 lower to 1.16 lower), very low-certainty evidence)

⑤ Postprandial blood glucose-lunch at 52 weeks: There is a small effect in reducing postprandial blood glucose. (RCT=1, N=323,MD 0.63 lower (1.21 lower to 0.05 lower), very low-certainty evidence)

⑥ Body weight change value (%, change value/baseline value) at 52 weeks: There is a trivial effect in reducing body weight.(RCT=1, N=323,MD 0.97 lower (2.12 lower to 0.18 higher), very low-certainty evidence)

⑦ Gastrointestinal disorders-Nausea at 52 weeks: There is a trivial effect in Gastrointestinal disorders-Nausea. (RCT=1, N=323,19 fewer per 1,000 (51 fewer to 54 more), very low-certainty evidence)

⑧ Gastrointestinal disorders-Vomiting at 52 weeks: There is a trivial effect in Gastrointestinal disorders-Vomiting. (RCT=1, N=323,1 fewer per 1,000 (34 fewer to 79 more), very low-certainty evidence)

⑨FPG change value (mmol/L) at 52 weeks: There is a large effect in reducing the FPG. (RCT=1, N=323,MD 1.77 lower (2.35 lower to 1.19 lower), very low-certainty evidence)

Other comments
② How substantial are the undesirable anticipated effects?

Undesirable effects

1)Critical outcome

① Incidence of nocturna hypolycemia at 26 weeks: There is a trivial effect in increasingthe incidence of hypoglycemia. (RCT=1, N=346,6 more per 1,000 (9 fewer to 90 more), low-certainty evidence)

② Incidence of hypoglycemia at 26 weeks: There is a large effect in increasingthe incidence of hypoglycemia. (RCT=1, N=343, 126 more per 1,000 (35 more to 320 more), low-certainty evidence)

2)Important outcome

① Gastrointestinal disorders-Diarrhea at 26 weeks: There is a trivial effect in Gastrointestinal disorders. (RCT=1, N=322,47 more per 1,000 (12 fewer to 168 more), low-certainty evidence)

② Gastrointestinal disorders-Diarrhea at 52 weeks: there is a trivial effect in Gastrointestinal disorders. (RCT=1, N=322,41 more per 1,000 (20 fewer to 156 more), low-certainty evidence)

Other comments
③ Is there important uncertainty about or variability in how much people value the main outcomes?
After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.
Other comments
④  Does the balance between desirable and undesirable effects favor the intervention or the comparison?
Other comments
⑤ Resources required
After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.
Other comments

⑥ What is the certainty of the evidence of resource requirements?

After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.
Other comments

⑦ Does the cost-effectiveness of the intervention favor the intervention or the comparison?

After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.
Other comments

⑧ What would be the impact on health equity?

After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.
Other comments

⑨ Is the intervention acceptable to key interest-holders?

After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.
Other comments

⑩ Is the intervention feasible to implement?

After a systematic literature search that yielded no relevant evidence, clinical experience is relied upon to inform the judgment.
Other comments

⑪ Type of recommendation?

Other comments
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