Download PowerPoint - 埼玉医科大学総合医療センター 内分泌・糖尿病内科

Journal Club
E.S. Mearns*1,2,W. J. Saulsberry 1,2, C. M. White 1,2, C. G. Kohn3 , S.
Lemieux1 , A. Sihabout1 , I. Salamucha1 and C. I. Coleman *1,2
Efficacy and safety of antihyperglycaemic drug regimens added to
metformin and sulphonylurea therapy in Type 2 diabetes: a network
meta-analysis
Diabetic Medicine. 2015 June. doi: 10.1111/dme.12837.
2015年7月30日 8:30-8:55
８階 医局
埼玉医科大学 総合医療センター 内分泌・糖尿病内科
Department of Endocrinology and Diabetes,
Saitama Medical Center, Saitama Medical University
Sellami Mnif Houda
ADA EASD Treatment Algorithm Type 2 Diabetes | NDEI
•This slide reviews recommendations for antihyperglycemic therapy for type 2 diabetes from the updated position statement of the American Diabetes Association and the European Association for
the Study of Diabetes (ADA/EASD).
Abbreviations:
DPP-4 inhibitor=dipeptidyl peptidase-4 inhibitor; GLP-1 RA=glucagon-like peptide-1 receptor agonist; MET=metformin; SGLT2 inhibitor=sodium glucose cotransporter 2 inhibitor; SU=sulfonylurea;
TZD=thiazolidinedione
Refer to source document for full recommendations.
•Received Date : 20-Dec-2014
•Revised Date : 01-Apr-2015
•Accepted Date : 19-Jun-2015
•Article type : Systematic Review or Meta-analysis
•Title: Diabetic Medicine
•Created by: Maria Davie
•Email proofs to: [email protected]
•Article no.: DME-2014-01019 Article type: Review Article
Review Article
Efficacy and safety of antihyperglycaemic drug regimens added to
metformin and sulphonylurea therapy in Type 2 diabetes: a network
meta-analysis
E. S. Mearns*1,2,W. J. Saulsberry 1,2, C. M. White1,2, C. G. Kohn3 , S.
Lemieux1 , A. Sihabout1 , I. Salamucha1 and C. I. Coleman *1,2
1 University of Connecticut School of Pharmacy, Department of Pharmacy Practice,
Storrs, 2 University of Connecticut/Hartford Hospital Evidence-Based Practice Center,
Hartford, and 3 University of Saint Joseph School of Pharmacy, Hartford, CT, USA
*These authors contributed equally to this meta-analysis.
Ann Neurol. 2015 May 14. doi: 10.1002/ana.24439.
Objective
To assess the efficacy and safety of thirdline adjuvant antihyperglycaemic agents in
people with Type 2 diabetes mellitus failing
metformin and sulphonylurea combination
therapy.
- To help clinicians to choose the optimum
therapy (reduction of HbA1C with less side
effects)
Methods
Performed a systematic literature search from the
earliest possible date–2014
Study selection
1- Published in English
2- Parallel RCT study
3- Comparing US/UE approved T2 Diabetes therapy
(including non insulin and/or long acting Basal insulin)
with another T2D drug therapy/ placebo
4- Only patients who showed inadequate response to
Metformin-SU therapy combination at randomization.
5- study (treatment) duration: 12-52 week
And report change in HbA1c,
6- Patients should be on Met+Su for at least 3 weeks
Data synthesis
- traditional
meta-analyses: changes in HbA1c, body weight
and SBP
- P value < 0.05
- Pairwise meta-analyses were performed for each AHA
- network
meta-analysis were performed:
analyze direct within-trial comparisons between two
treatments
+
enables incorporation of indirect comparisons
constructed from two trials that have one treatment in
common
FIGURE 1 Results of the literature search. CCTR, Cochrane Controlled Trials Register; EU, European Union; FDA, US Food and Drug
Administration; SU, sulphonylurea.
FIGURE 2 Network diagram of randomized controlled trials evaluating antihyperglycaemic agents in addition to metformin and a sulphonylurea in Type 2 diabetes. All
therapies are in combination with metformin and a sulphonylurea. Lines represent the presence of direct comparison trial(s). All direct comparisons were based upon a
single study; except where otherwise indicated.
RESULTS:
Characteristics of the included trials:
1. - The trial duration range : 16–52 weeks
2. - Mean age: 41–67 years
3. BMI 24–35 kg/m2
4. Weight 65–99 kg
5. SBP 127–146 mmHg
6. Baseline HbA1c: 64–80 mmol/mol (8.0–9.5%).
Main ending points:
1-Change in HbA1c
All AHAs significantly lowered HbA1c from baseline but by different magnitudes
2- Body weight
Only SGLT2 inhibitors showed statistically significant weight loss compared
with placebo/control (1.43–2.07 kg)
TZDs, glargine and sitagliptin : significant weight gain compared with placebo/control
3- Systolic blood pressure
•Rosiglitazone, liraglutide and all SGLT2 inhibitors: significantly decreased SBP
compared with placebo/control (2.93–6.83 mmHg).
•Pioglitazone, sitagliptin and insulin glargine : neutral effect
In active drug comparisons:
•Rosiglitazone significantly reduced SBP compared with all other therapies analyzed
(3.43–9.38 mmHg) except dapagliflozin ( similar reduction).
•All SLGT2 inhibitors and liraglutide were associated with a significant decrease in
SBP compared with pioglitazone, insulin glargine and sitagliptin
•No data were available for acarbose, exenatide, linagliptin, saxagliptin or vildagliptin
4-Confirmed hypoGlycemia
•TZDs, glargine, sitagliptin, liraglutide, and canagliflozin : significantly higher
rates of confirmed hypoglycaemia compared with placebo/control
•Empagliflozin, exenatide and DPP-4 inhibitors (with the exception of
sitagliptin) were not.
•In active drug comparisons: Glargine and Rosiglitazone significant higher rate
of confirmed hypoglycaemia compared with the SGLT-2 In, exenatide, linagliptin
and sitagliptin
5- Urinary and genital tract infections
•No data evaluating (acarbose, pioglitazone and rosiglitazone) for the UTI
•Only four of the 13 agents (all SGLT2 inhibitors and sitagliptin) reported on
GTI. No evaluable therapy was associated with an increased risk of UTI when
compared with placebo/control and
•only canagliflozin was associated with a greater risk of GTI compared with
placebo/control (relative risk 3.9, 95% CI 1.58--9.6) and sitagliptin (relative risk
5.64, 95% CI 2.68–11.88)
Direct and indirect meta-analysis coherence
Comparing the results of the 36 possible direct and
indirect effect estimates across all six endpoints
Evidence of incoherence for only two comparisons;
both for the body weight endpoint
(canagliflozin–sitagliptin–placebo)
and
(pioglitazone–sitagliptin–placebo).
INTERPRETATION
- For peoples with strong apprehension about needles and self injections
oral agents, such as SGLT2 inhibitors, maybe a better choice for them
This meta-analysis suggests patients can be prescribed many oral agents with
minimal sacrifice of glycaemic efficacy.
-T2D high risk of albuminuria (Diabetes+Obesity+HBP)
SGLT2 inhibitors,rosiglitazone and liraglutide have better BP reduction.
SGLT2 inhibitors+++, GLP-1 analogues and acarbose Weight reduction
-T2D (mostly women): high risk of UTI and GTI, however we did not find a greater
risk of UTIs for SGLT2 Inh class (despite its Urine Tract action) or any other
evaluable agent compared with placebo/control
LIMITATIONS
-Don’t assess other endpoints: CV events, Pancreatitis, GI effects..
- Some AHA were compared on only 1-2 trials
- Most trials followed patients for 24 Weeks
- Can not exclude the presence of incoherence in the network
- The quality of trial reporting and conduct varied between studies,
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