Prognostic role of metformin in diabetes mellitus type 2 patients with hepatocellular carcinoma: A systematic review and meta-analysis

Table 1 Characteristics of included studies for the risk of overall cause of death

Ref.	City	Country	Study period	Design	N	Therapy	DM (no metformin)	Number of events	DM (metformin)	Number of events
Chen et al[29], 2011	Taichung	Taiwan	June 2003 to July 2009	Retro	53	RFA	32	18	21	6
Bhat et al[25], 2014	Rochester	United States	January 2005 to June 2011	Retro	263	No therapy	207	133	56	37
Jang et al[30], 2015	Seoul	Korea	March 2003 to December 2012	Retro	48	RT	29	13	19	5
Casadei Gardini et al[31], 2015	Meldola	Italy	March 2008 to August 2014	Retro	42	Sorafenib	11	5	31	22
Seo et al[32], 2016	Seoul	Korea	January 2005 to December 2011	Retro	751	HR	218	111	533	169
Chan et al[33], 2017	Taipei	Taiwan	January 1995 to December 2011	Retro	4610	HR	2978	1335	1632	612
					7813	No surgery	5884	3858	1929	1437
Casadei Gardini et al[24], 2017	Meldola	Italy	May 2007 to September 2015	Retro	86	Sorafenib	34	26	52	45
Chung et al[34], 2018	Seoul	Korea	January 2009 to December 2016	Retro	63	Sorafenib + HR	23	23	40	30
					31	Sorafenib + LT	17	14	14	13
Luo et al[26], 2020	Nanchang	China	January 2000 to December 2013	Retro	250	HR	184	129	66	49
Cho et al[35], 2021	Kaohsiung	Taiwan	April 2001 to June 2016	Retro	222	HR	86	15	136	26
Tangjarusritaratorn et al[36], 2021	Bangkok	Thailand	January 2006 to June 2014	Prosp	327	Multiple therapies	165	84	162	60
Elsayed et al[37], 2021	Atlanta	United States	2014-2018	Retro	40	TARE	21	8	19	8
Hydes et al[38], 2022	Birmingham	United Kingdom	January 2007 to March 2012	Prosp	287	Multiple therapies	139	58	148	63
Total					14886		10028	5830	4858	2582

DM: Diabetes mellitus; Retro: Retrospective; Prosp: Prospective; RFA: Radiofrequency ablation; RT: Radiotherapy; HR: Hepatic resection; LT: Liver transplantation; TARE: Trans-arterial radio-embolization.

Table 2 Characteristics of included studies for the risk of progressive tumor disease

Ref.	City	Country	Study period	Design	N	Therapy	DM (no metformin)	Number of events	DM (metformin)	Number of events
Jang et al[30], 2015	Seoul	Korea	March 2003 to December 2012	Retro	48	RT	29	24	19	9
Casadei Gardini et al[31], 2015	Meldola	Italy	March 2008 to August 2014	Retro	42	Sorafenib	11	9	31	28
Casadei Gardini et al[24], 2017	Meldola	Italy	May 2007 to September 2015	Retro	86	Sorafenib	34	33	52	47
Chung et al[34], 2018	Seoul	Korea	January 2009 to December 2016	Retro	63	Sorafenib + HR	23	23	40	40
					31	Sorafenib + LT	17	17	14	14
Total					270		114	106	156	138

DM: Diabetes mellitus; Retro: Retrospective; RT: Radiotherapy; HR: Hepatic resection; LT: Liver transplantation.

Table 3 Characteristics of included studies for the risk of hepatocellular carcinoma recurrence

Ref.	City	Country	Study period	Design	N	Therapy	DM (no metformin)	Number of events	DM (metformin)	Number of events
Chen et al[29], 2011	Taichung	Taiwan	June 2003 to July 2009	Retro	53	RFA	32	18	21	12
Chan et al[33], 2017	Taipei	Taiwan	January 1995 to December 2011	Retro	4610	HR	2978	1615	1632	698
					7813	No surgery	5884	2668	1929	982
Cho et al[35], 2021	Kaohsiung	Taiwan	April 2001 to June 2016	Retro	222	HR	86	52	136	85
Total					12698		8980	4353	3718	1777

DM: Diabetes mellitus; Retro: Retrospective; RFA: Radiofrequency ablation; HR: Hepatic resection.