Efficacy and Safety of Pioglitazone Add‐On in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin and Dapagliflozin: A Systematic Review and Meta‐Analysis of Randomised Controlled Trials
ABSTRACT Background Type 2 diabetes mellitus (T2DM) accounts for over 90% of diabetes cases worldwide. Pioglitazone, a thiazolidinedione, enhances insulin sensitivity by activating PPAR‐γ. Evidence on its efficacy and safety as an add‐on to metformin and SGLT2 inhibitors in inadequately controlled T...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-05-01
|
| Series: | Endocrinology, Diabetes & Metabolism |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/edm2.70061 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849763121679302656 |
|---|---|
| author | Ubaid Khan Zuhair Majeed Muhammad Haris Khan Ahmed Bostamy Elsnhory Ahmed Mazen Amin Anum Nawaz Ahmed Raza Hafiz Muhammad Waqas Siddque Mustafa Turkmani Mohamed Abuelazm |
| author_facet | Ubaid Khan Zuhair Majeed Muhammad Haris Khan Ahmed Bostamy Elsnhory Ahmed Mazen Amin Anum Nawaz Ahmed Raza Hafiz Muhammad Waqas Siddque Mustafa Turkmani Mohamed Abuelazm |
| author_sort | Ubaid Khan |
| collection | DOAJ |
| description | ABSTRACT Background Type 2 diabetes mellitus (T2DM) accounts for over 90% of diabetes cases worldwide. Pioglitazone, a thiazolidinedione, enhances insulin sensitivity by activating PPAR‐γ. Evidence on its efficacy and safety as an add‐on to metformin and SGLT2 inhibitors in inadequately controlled T2DM is limited. This systematic review and meta‐analysis evaluates pioglitazone's role as a third‐line therapy for improving glycaemic control in addition to metformin and Dapagliflozin. Methodology We conducted comprehensive searches across PubMed, CENTRAL, WOS, Scopus and EMBASE until December 2024. Pooled data were reported using risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, along with a 95% confidence interval (CI). This systematic review and meta‐analysis is registered with PROSPERO ID: CRD42024612005. Results We included three RCTs with 885 patients. Pioglitazone add‐on therapy significantly reduced HbA1c levels (MD: −0.41; 95% CI: −0.54 to −0.27, p = < 0.00001, I2 = 0%), fasting blood glucose (MD: −11.91; 95% CI: −16.34 to −7.48, p = < 0.00001, I2 = 0%), Homeostatic Model Assessment for Insulin Resistance (HOMA‐IR) (MD: −0.65; 95% CI: −1.05 to −0.25, p = 0.001, I2 = 4.89%), increased the rate of achieving HbA1c < 7% (RR: 2.09; 95% CI: 1.66 to 2.64, p = < 0.00001, I2 = 0%), and HbA1c < 6.5% (RR: 2.19; 95% CI: 1.36 to 3.53, p = 0.001, I2 = 0%). However, there was no difference regarding Homeostasis model assessment of β‐cell function (HOMA‐β) between the two groups (MD: 2.73; 95% CI: −5.24 to 10.70, p = 0.5, I2 = 27.53%). Conclusion Pioglitazone add‐on therapy significantly improved glycaemic control by reducing HbA1c, fasting blood glucose and HOMA‐IR while increasing the likelihood of achieving HbA1c targets. However, no significant difference was observed in HOMA‐β between groups. These findings suggest the potential benefit of pioglitazone in enhancing glycaemic outcomes in diabetes management. |
| format | Article |
| id | doaj-art-5f62ce79c8ff47c6b13db06768b77a9a |
| institution | DOAJ |
| issn | 2398-9238 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Endocrinology, Diabetes & Metabolism |
| spelling | doaj-art-5f62ce79c8ff47c6b13db06768b77a9a2025-08-20T03:05:30ZengWileyEndocrinology, Diabetes & Metabolism2398-92382025-05-0183n/an/a10.1002/edm2.70061Efficacy and Safety of Pioglitazone Add‐On in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin and Dapagliflozin: A Systematic Review and Meta‐Analysis of Randomised Controlled TrialsUbaid Khan0Zuhair Majeed1Muhammad Haris Khan2Ahmed Bostamy Elsnhory3Ahmed Mazen Amin4Anum Nawaz5Ahmed Raza6Hafiz Muhammad Waqas Siddque7Mustafa Turkmani8Mohamed Abuelazm9Division of Cardiology University of Maryland School of Medicine Baltimore Maryland USADepartment of Medicine King Edward Medical University Lahore PakistanDepartment of Medicine Saidu Medical College Swat PakistanEmergency Medicine Department Al‐Bank Al‐Ahly Hospital Cairo EgyptFaculty of Medicine Mansoura University Mansoura EgyptDepartment of Radiology Pakistan Atomic Energy Commission Hospital Islamabad PakistanDepartment of Medicine Services Institute of Medical Sciences Lahore PakistanDepartment of Medicine MedStar Health Georgetown University (Baltimore) Program Baltimore Maryland USAFaculty of Medicine Michigan State University East Lansing Michigan USAFaculty of Medicine Tanta University Tanta EgyptABSTRACT Background Type 2 diabetes mellitus (T2DM) accounts for over 90% of diabetes cases worldwide. Pioglitazone, a thiazolidinedione, enhances insulin sensitivity by activating PPAR‐γ. Evidence on its efficacy and safety as an add‐on to metformin and SGLT2 inhibitors in inadequately controlled T2DM is limited. This systematic review and meta‐analysis evaluates pioglitazone's role as a third‐line therapy for improving glycaemic control in addition to metformin and Dapagliflozin. Methodology We conducted comprehensive searches across PubMed, CENTRAL, WOS, Scopus and EMBASE until December 2024. Pooled data were reported using risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, along with a 95% confidence interval (CI). This systematic review and meta‐analysis is registered with PROSPERO ID: CRD42024612005. Results We included three RCTs with 885 patients. Pioglitazone add‐on therapy significantly reduced HbA1c levels (MD: −0.41; 95% CI: −0.54 to −0.27, p = < 0.00001, I2 = 0%), fasting blood glucose (MD: −11.91; 95% CI: −16.34 to −7.48, p = < 0.00001, I2 = 0%), Homeostatic Model Assessment for Insulin Resistance (HOMA‐IR) (MD: −0.65; 95% CI: −1.05 to −0.25, p = 0.001, I2 = 4.89%), increased the rate of achieving HbA1c < 7% (RR: 2.09; 95% CI: 1.66 to 2.64, p = < 0.00001, I2 = 0%), and HbA1c < 6.5% (RR: 2.19; 95% CI: 1.36 to 3.53, p = 0.001, I2 = 0%). However, there was no difference regarding Homeostasis model assessment of β‐cell function (HOMA‐β) between the two groups (MD: 2.73; 95% CI: −5.24 to 10.70, p = 0.5, I2 = 27.53%). Conclusion Pioglitazone add‐on therapy significantly improved glycaemic control by reducing HbA1c, fasting blood glucose and HOMA‐IR while increasing the likelihood of achieving HbA1c targets. However, no significant difference was observed in HOMA‐β between groups. These findings suggest the potential benefit of pioglitazone in enhancing glycaemic outcomes in diabetes management.https://doi.org/10.1002/edm2.70061dapagliflozinmetforminpioglitazonereviewtype 2 diabetes mellitus |
| spellingShingle | Ubaid Khan Zuhair Majeed Muhammad Haris Khan Ahmed Bostamy Elsnhory Ahmed Mazen Amin Anum Nawaz Ahmed Raza Hafiz Muhammad Waqas Siddque Mustafa Turkmani Mohamed Abuelazm Efficacy and Safety of Pioglitazone Add‐On in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin and Dapagliflozin: A Systematic Review and Meta‐Analysis of Randomised Controlled Trials Endocrinology, Diabetes & Metabolism dapagliflozin metformin pioglitazone review type 2 diabetes mellitus |
| title | Efficacy and Safety of Pioglitazone Add‐On in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin and Dapagliflozin: A Systematic Review and Meta‐Analysis of Randomised Controlled Trials |
| title_full | Efficacy and Safety of Pioglitazone Add‐On in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin and Dapagliflozin: A Systematic Review and Meta‐Analysis of Randomised Controlled Trials |
| title_fullStr | Efficacy and Safety of Pioglitazone Add‐On in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin and Dapagliflozin: A Systematic Review and Meta‐Analysis of Randomised Controlled Trials |
| title_full_unstemmed | Efficacy and Safety of Pioglitazone Add‐On in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin and Dapagliflozin: A Systematic Review and Meta‐Analysis of Randomised Controlled Trials |
| title_short | Efficacy and Safety of Pioglitazone Add‐On in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin and Dapagliflozin: A Systematic Review and Meta‐Analysis of Randomised Controlled Trials |
| title_sort | efficacy and safety of pioglitazone add on in patients with type 2 diabetes mellitus inadequately controlled with metformin and dapagliflozin a systematic review and meta analysis of randomised controlled trials |
| topic | dapagliflozin metformin pioglitazone review type 2 diabetes mellitus |
| url | https://doi.org/10.1002/edm2.70061 |
| work_keys_str_mv | AT ubaidkhan efficacyandsafetyofpioglitazoneaddoninpatientswithtype2diabetesmellitusinadequatelycontrolledwithmetforminanddapagliflozinasystematicreviewandmetaanalysisofrandomisedcontrolledtrials AT zuhairmajeed efficacyandsafetyofpioglitazoneaddoninpatientswithtype2diabetesmellitusinadequatelycontrolledwithmetforminanddapagliflozinasystematicreviewandmetaanalysisofrandomisedcontrolledtrials AT muhammadhariskhan efficacyandsafetyofpioglitazoneaddoninpatientswithtype2diabetesmellitusinadequatelycontrolledwithmetforminanddapagliflozinasystematicreviewandmetaanalysisofrandomisedcontrolledtrials AT ahmedbostamyelsnhory efficacyandsafetyofpioglitazoneaddoninpatientswithtype2diabetesmellitusinadequatelycontrolledwithmetforminanddapagliflozinasystematicreviewandmetaanalysisofrandomisedcontrolledtrials AT ahmedmazenamin efficacyandsafetyofpioglitazoneaddoninpatientswithtype2diabetesmellitusinadequatelycontrolledwithmetforminanddapagliflozinasystematicreviewandmetaanalysisofrandomisedcontrolledtrials AT anumnawaz efficacyandsafetyofpioglitazoneaddoninpatientswithtype2diabetesmellitusinadequatelycontrolledwithmetforminanddapagliflozinasystematicreviewandmetaanalysisofrandomisedcontrolledtrials AT ahmedraza efficacyandsafetyofpioglitazoneaddoninpatientswithtype2diabetesmellitusinadequatelycontrolledwithmetforminanddapagliflozinasystematicreviewandmetaanalysisofrandomisedcontrolledtrials AT hafizmuhammadwaqassiddque efficacyandsafetyofpioglitazoneaddoninpatientswithtype2diabetesmellitusinadequatelycontrolledwithmetforminanddapagliflozinasystematicreviewandmetaanalysisofrandomisedcontrolledtrials AT mustafaturkmani efficacyandsafetyofpioglitazoneaddoninpatientswithtype2diabetesmellitusinadequatelycontrolledwithmetforminanddapagliflozinasystematicreviewandmetaanalysisofrandomisedcontrolledtrials AT mohamedabuelazm efficacyandsafetyofpioglitazoneaddoninpatientswithtype2diabetesmellitusinadequatelycontrolledwithmetforminanddapagliflozinasystematicreviewandmetaanalysisofrandomisedcontrolledtrials |