Loading…
Efficacy and tolerability of initial triple combination therapy with metformin, dapagliflozin and saxagliptin compared with stepwise add‐on therapy in drug‐naïve patients with type 2 diabetes (TRIPLE‐AXEL study): A multicentre, randomized, 104‐week, open‐label, active‐controlled trial
Aim To evaluate the efficacy and tolerability of an initial triple combination therapy (TCT) compared with conventional stepwise add‐on therapy (SAT) in patients with newly diagnosed type 2 diabetes (T2D). Materials and Methods This multicentre, randomized, 104‐week, open‐label trial randomized 105...
Saved in:
| Published in: | Diabetes, obesity & metabolism obesity & metabolism, 2024-09, Vol.26 (9), p.3642-3652 |
|---|---|
| Main Authors: | , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | |
|---|---|
| cites | cdi_FETCH-LOGICAL-c2785-8d6d13994c03ea6bf282ca4637bc0730359727451601a9124edf7ad31b9716163 |
| container_end_page | 3652 |
| container_issue | 9 |
| container_start_page | 3642 |
| container_title | Diabetes, obesity & metabolism |
| container_volume | 26 |
| creator | Kim, Nam Hoon Moon, Jun Sung Lee, Yong‐ho Cho, Ho Chan Kwak, Soo Heon Lim, Soo Moon, Min Kyong Kim, Dong‐Lim Kim, Tae Ho Ko, Eunvin Lee, Juneyoung Kim, Sin Gon |
| description | Aim
To evaluate the efficacy and tolerability of an initial triple combination therapy (TCT) compared with conventional stepwise add‐on therapy (SAT) in patients with newly diagnosed type 2 diabetes (T2D).
Materials and Methods
This multicentre, randomized, 104‐week, open‐label trial randomized 105 patients with drug‐naïve T2D (with HbA1c level ≥ 8.0%, |
| doi_str_mv | 10.1111/dom.15705 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3066336145</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3087919161</sourcerecordid><originalsourceid>FETCH-LOGICAL-c2785-8d6d13994c03ea6bf282ca4637bc0730359727451601a9124edf7ad31b9716163</originalsourceid><addsrcrecordid>eNp1kk1u1DAUgAMC0VJYcAFkiU2LMq0d55fdqAxQaVARKhK7yLFfWhcnDrbTIV1xBG7CIbgJJ-F1UhBCwhv7Wd_7_Gy_KHrC6CHDcaRsd8iygmZ3o12W5nzBeJLf266TRVnRZCd66P0lpTTlZfEg2uFlmfEiobt3nq_aVkshJyJ6RYI14ESjjQ4TsS3RvQ5aGBKcHgwQabtG9yJo25NwgeQwkY0OF6SD0FrX6T4mSgzi3OjW2Gvdb6VefLnZGQLGaBiEAzWn-QDDRnsgQqmfX7_9ZUVUufEcN3vx4_sVkAFPhT74OTFMA5CEKC0aCODJ_tn7k3frFeLLj6s1ekc1HbwgS9KNJmiJiQ5i4rAa2-lrUDFhNEV6A_ApJnaAHgODMhMTIYO-AoylxTRrDFaL9xfmUXS_FcbD49t5L_rwanV2_GaxPn19crxcL2RSlNmiVLlivKpSSTmIvGmTMpECf6VoJC045VlVJEWasZwyUbEkBdUWQnHWVAXLWc73ov3ZOzj7eQQf6k57CcaIHuzoa07znPOcpRmiz_5BL-3oeqwOqbKoWIVGpA5mSjrrvYO2HpzuhJtqRuubBqrxWeptAyH79NY4Nh2oP-TvjkHgaAY22sD0f1P98vTtrPwFtznaFQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3087919161</pqid></control><display><type>article</type><title>Efficacy and tolerability of initial triple combination therapy with metformin, dapagliflozin and saxagliptin compared with stepwise add‐on therapy in drug‐naïve patients with type 2 diabetes (TRIPLE‐AXEL study): A multicentre, randomized, 104‐week, open‐label, active‐controlled trial</title><source>Wiley</source><creator>Kim, Nam Hoon ; Moon, Jun Sung ; Lee, Yong‐ho ; Cho, Ho Chan ; Kwak, Soo Heon ; Lim, Soo ; Moon, Min Kyong ; Kim, Dong‐Lim ; Kim, Tae Ho ; Ko, Eunvin ; Lee, Juneyoung ; Kim, Sin Gon</creator><creatorcontrib>Kim, Nam Hoon ; Moon, Jun Sung ; Lee, Yong‐ho ; Cho, Ho Chan ; Kwak, Soo Heon ; Lim, Soo ; Moon, Min Kyong ; Kim, Dong‐Lim ; Kim, Tae Ho ; Ko, Eunvin ; Lee, Juneyoung ; Kim, Sin Gon</creatorcontrib><description>Aim
To evaluate the efficacy and tolerability of an initial triple combination therapy (TCT) compared with conventional stepwise add‐on therapy (SAT) in patients with newly diagnosed type 2 diabetes (T2D).
Materials and Methods
This multicentre, randomized, 104‐week, open‐label trial randomized 105 patients with drug‐naïve T2D (with HbA1c level ≥ 8.0%, < 11.0%) to the TCT (1000 mg of metformin, 10 mg of dapagliflozin and 5 mg of saxagliptin once daily) or SAT (initiated with metformin, followed by glimepiride and sitagliptin) groups. The primary outcome was the proportion of patients who achieved an HbA1c level of less than 6.5% without hypoglycaemia, weight gain of 5% or higher, or discontinuation of drugs because of adverse events at week 104.
Results
HbA1c reduction from baseline at week 104 was similar between the groups (the least squares mean change was −2.56% in the TCT group vs. –2.75% in the SAT group). The primary outcome was achieved in 39.0% and 17.1% of the TCT and SAT groups, respectively, with a risk difference of 22.0 (95% confidence interval 3.0, 40.8; P = .027). HbA1c level less than 6.5% at week 104 was 46.3% in both the TCT and SAT groups, whereas the incidence of hypoglycaemia, weight gain, or discontinuation of drugs was 16.7% and 62.0% in the TCT and SAT groups, respectively (P < .001). TCT was well‐tolerated and had fewer adverse events than SAT.
Conclusions
Among newly diagnosed patients with T2D, initial TCT effectively lowered HbA1c levels with higher tolerability and safety than SAT for 104 weeks, suggesting a novel strategy for initial combination therapy in T2D patients.</description><identifier>ISSN: 1462-8902</identifier><identifier>ISSN: 1463-1326</identifier><identifier>EISSN: 1463-1326</identifier><identifier>DOI: 10.1111/dom.15705</identifier><identifier>PMID: 38853720</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adverse events ; Antidiabetics ; clinical trial ; Combination therapy ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; DPP‐4 inhibitor ; glycaemic control ; Hypoglycemia ; Metformin ; SGLT2 inhibitor ; type 2 diabetes</subject><ispartof>Diabetes, obesity & metabolism, 2024-09, Vol.26 (9), p.3642-3652</ispartof><rights>2024 The Author(s). published by John Wiley & Sons Ltd.</rights><rights>2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.</rights><rights>2024. This article is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2785-8d6d13994c03ea6bf282ca4637bc0730359727451601a9124edf7ad31b9716163</cites><orcidid>0000-0002-4137-1671 ; 0000-0002-7430-3675 ; 0000-0002-9926-1344 ; 0000-0002-5460-2846 ; 0000-0002-6219-4942 ; 0000-0003-1569-3068</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38853720$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Nam Hoon</creatorcontrib><creatorcontrib>Moon, Jun Sung</creatorcontrib><creatorcontrib>Lee, Yong‐ho</creatorcontrib><creatorcontrib>Cho, Ho Chan</creatorcontrib><creatorcontrib>Kwak, Soo Heon</creatorcontrib><creatorcontrib>Lim, Soo</creatorcontrib><creatorcontrib>Moon, Min Kyong</creatorcontrib><creatorcontrib>Kim, Dong‐Lim</creatorcontrib><creatorcontrib>Kim, Tae Ho</creatorcontrib><creatorcontrib>Ko, Eunvin</creatorcontrib><creatorcontrib>Lee, Juneyoung</creatorcontrib><creatorcontrib>Kim, Sin Gon</creatorcontrib><title>Efficacy and tolerability of initial triple combination therapy with metformin, dapagliflozin and saxagliptin compared with stepwise add‐on therapy in drug‐naïve patients with type 2 diabetes (TRIPLE‐AXEL study): A multicentre, randomized, 104‐week, open‐label, active‐controlled trial</title><title>Diabetes, obesity & metabolism</title><addtitle>Diabetes Obes Metab</addtitle><description>Aim
To evaluate the efficacy and tolerability of an initial triple combination therapy (TCT) compared with conventional stepwise add‐on therapy (SAT) in patients with newly diagnosed type 2 diabetes (T2D).
Materials and Methods
This multicentre, randomized, 104‐week, open‐label trial randomized 105 patients with drug‐naïve T2D (with HbA1c level ≥ 8.0%, < 11.0%) to the TCT (1000 mg of metformin, 10 mg of dapagliflozin and 5 mg of saxagliptin once daily) or SAT (initiated with metformin, followed by glimepiride and sitagliptin) groups. The primary outcome was the proportion of patients who achieved an HbA1c level of less than 6.5% without hypoglycaemia, weight gain of 5% or higher, or discontinuation of drugs because of adverse events at week 104.
Results
HbA1c reduction from baseline at week 104 was similar between the groups (the least squares mean change was −2.56% in the TCT group vs. –2.75% in the SAT group). The primary outcome was achieved in 39.0% and 17.1% of the TCT and SAT groups, respectively, with a risk difference of 22.0 (95% confidence interval 3.0, 40.8; P = .027). HbA1c level less than 6.5% at week 104 was 46.3% in both the TCT and SAT groups, whereas the incidence of hypoglycaemia, weight gain, or discontinuation of drugs was 16.7% and 62.0% in the TCT and SAT groups, respectively (P < .001). TCT was well‐tolerated and had fewer adverse events than SAT.
Conclusions
Among newly diagnosed patients with T2D, initial TCT effectively lowered HbA1c levels with higher tolerability and safety than SAT for 104 weeks, suggesting a novel strategy for initial combination therapy in T2D patients.</description><subject>Adverse events</subject><subject>Antidiabetics</subject><subject>clinical trial</subject><subject>Combination therapy</subject><subject>Diabetes</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>DPP‐4 inhibitor</subject><subject>glycaemic control</subject><subject>Hypoglycemia</subject><subject>Metformin</subject><subject>SGLT2 inhibitor</subject><subject>type 2 diabetes</subject><issn>1462-8902</issn><issn>1463-1326</issn><issn>1463-1326</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><recordid>eNp1kk1u1DAUgAMC0VJYcAFkiU2LMq0d55fdqAxQaVARKhK7yLFfWhcnDrbTIV1xBG7CIbgJJ-F1UhBCwhv7Wd_7_Gy_KHrC6CHDcaRsd8iygmZ3o12W5nzBeJLf266TRVnRZCd66P0lpTTlZfEg2uFlmfEiobt3nq_aVkshJyJ6RYI14ESjjQ4TsS3RvQ5aGBKcHgwQabtG9yJo25NwgeQwkY0OF6SD0FrX6T4mSgzi3OjW2Gvdb6VefLnZGQLGaBiEAzWn-QDDRnsgQqmfX7_9ZUVUufEcN3vx4_sVkAFPhT74OTFMA5CEKC0aCODJ_tn7k3frFeLLj6s1ekc1HbwgS9KNJmiJiQ5i4rAa2-lrUDFhNEV6A_ApJnaAHgODMhMTIYO-AoylxTRrDFaL9xfmUXS_FcbD49t5L_rwanV2_GaxPn19crxcL2RSlNmiVLlivKpSSTmIvGmTMpECf6VoJC045VlVJEWasZwyUbEkBdUWQnHWVAXLWc73ov3ZOzj7eQQf6k57CcaIHuzoa07znPOcpRmiz_5BL-3oeqwOqbKoWIVGpA5mSjrrvYO2HpzuhJtqRuubBqrxWeptAyH79NY4Nh2oP-TvjkHgaAY22sD0f1P98vTtrPwFtznaFQ</recordid><startdate>202409</startdate><enddate>202409</enddate><creator>Kim, Nam Hoon</creator><creator>Moon, Jun Sung</creator><creator>Lee, Yong‐ho</creator><creator>Cho, Ho Chan</creator><creator>Kwak, Soo Heon</creator><creator>Lim, Soo</creator><creator>Moon, Min Kyong</creator><creator>Kim, Dong‐Lim</creator><creator>Kim, Tae Ho</creator><creator>Ko, Eunvin</creator><creator>Lee, Juneyoung</creator><creator>Kim, Sin Gon</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4137-1671</orcidid><orcidid>https://orcid.org/0000-0002-7430-3675</orcidid><orcidid>https://orcid.org/0000-0002-9926-1344</orcidid><orcidid>https://orcid.org/0000-0002-5460-2846</orcidid><orcidid>https://orcid.org/0000-0002-6219-4942</orcidid><orcidid>https://orcid.org/0000-0003-1569-3068</orcidid></search><sort><creationdate>202409</creationdate><title>Efficacy and tolerability of initial triple combination therapy with metformin, dapagliflozin and saxagliptin compared with stepwise add‐on therapy in drug‐naïve patients with type 2 diabetes (TRIPLE‐AXEL study): A multicentre, randomized, 104‐week, open‐label, active‐controlled trial</title><author>Kim, Nam Hoon ; Moon, Jun Sung ; Lee, Yong‐ho ; Cho, Ho Chan ; Kwak, Soo Heon ; Lim, Soo ; Moon, Min Kyong ; Kim, Dong‐Lim ; Kim, Tae Ho ; Ko, Eunvin ; Lee, Juneyoung ; Kim, Sin Gon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2785-8d6d13994c03ea6bf282ca4637bc0730359727451601a9124edf7ad31b9716163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adverse events</topic><topic>Antidiabetics</topic><topic>clinical trial</topic><topic>Combination therapy</topic><topic>Diabetes</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>DPP‐4 inhibitor</topic><topic>glycaemic control</topic><topic>Hypoglycemia</topic><topic>Metformin</topic><topic>SGLT2 inhibitor</topic><topic>type 2 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Nam Hoon</creatorcontrib><creatorcontrib>Moon, Jun Sung</creatorcontrib><creatorcontrib>Lee, Yong‐ho</creatorcontrib><creatorcontrib>Cho, Ho Chan</creatorcontrib><creatorcontrib>Kwak, Soo Heon</creatorcontrib><creatorcontrib>Lim, Soo</creatorcontrib><creatorcontrib>Moon, Min Kyong</creatorcontrib><creatorcontrib>Kim, Dong‐Lim</creatorcontrib><creatorcontrib>Kim, Tae Ho</creatorcontrib><creatorcontrib>Ko, Eunvin</creatorcontrib><creatorcontrib>Lee, Juneyoung</creatorcontrib><creatorcontrib>Kim, Sin Gon</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library Free Content</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetes, obesity & metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Nam Hoon</au><au>Moon, Jun Sung</au><au>Lee, Yong‐ho</au><au>Cho, Ho Chan</au><au>Kwak, Soo Heon</au><au>Lim, Soo</au><au>Moon, Min Kyong</au><au>Kim, Dong‐Lim</au><au>Kim, Tae Ho</au><au>Ko, Eunvin</au><au>Lee, Juneyoung</au><au>Kim, Sin Gon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy and tolerability of initial triple combination therapy with metformin, dapagliflozin and saxagliptin compared with stepwise add‐on therapy in drug‐naïve patients with type 2 diabetes (TRIPLE‐AXEL study): A multicentre, randomized, 104‐week, open‐label, active‐controlled trial</atitle><jtitle>Diabetes, obesity & metabolism</jtitle><addtitle>Diabetes Obes Metab</addtitle><date>2024-09</date><risdate>2024</risdate><volume>26</volume><issue>9</issue><spage>3642</spage><epage>3652</epage><pages>3642-3652</pages><issn>1462-8902</issn><issn>1463-1326</issn><eissn>1463-1326</eissn><abstract>Aim
To evaluate the efficacy and tolerability of an initial triple combination therapy (TCT) compared with conventional stepwise add‐on therapy (SAT) in patients with newly diagnosed type 2 diabetes (T2D).
Materials and Methods
This multicentre, randomized, 104‐week, open‐label trial randomized 105 patients with drug‐naïve T2D (with HbA1c level ≥ 8.0%, < 11.0%) to the TCT (1000 mg of metformin, 10 mg of dapagliflozin and 5 mg of saxagliptin once daily) or SAT (initiated with metformin, followed by glimepiride and sitagliptin) groups. The primary outcome was the proportion of patients who achieved an HbA1c level of less than 6.5% without hypoglycaemia, weight gain of 5% or higher, or discontinuation of drugs because of adverse events at week 104.
Results
HbA1c reduction from baseline at week 104 was similar between the groups (the least squares mean change was −2.56% in the TCT group vs. –2.75% in the SAT group). The primary outcome was achieved in 39.0% and 17.1% of the TCT and SAT groups, respectively, with a risk difference of 22.0 (95% confidence interval 3.0, 40.8; P = .027). HbA1c level less than 6.5% at week 104 was 46.3% in both the TCT and SAT groups, whereas the incidence of hypoglycaemia, weight gain, or discontinuation of drugs was 16.7% and 62.0% in the TCT and SAT groups, respectively (P < .001). TCT was well‐tolerated and had fewer adverse events than SAT.
Conclusions
Among newly diagnosed patients with T2D, initial TCT effectively lowered HbA1c levels with higher tolerability and safety than SAT for 104 weeks, suggesting a novel strategy for initial combination therapy in T2D patients.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>38853720</pmid><doi>10.1111/dom.15705</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-4137-1671</orcidid><orcidid>https://orcid.org/0000-0002-7430-3675</orcidid><orcidid>https://orcid.org/0000-0002-9926-1344</orcidid><orcidid>https://orcid.org/0000-0002-5460-2846</orcidid><orcidid>https://orcid.org/0000-0002-6219-4942</orcidid><orcidid>https://orcid.org/0000-0003-1569-3068</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1462-8902 |
| ispartof | Diabetes, obesity & metabolism, 2024-09, Vol.26 (9), p.3642-3652 |
| issn | 1462-8902 1463-1326 1463-1326 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_3066336145 |
| source | Wiley |
| subjects | Adverse events Antidiabetics clinical trial Combination therapy Diabetes Diabetes mellitus (non-insulin dependent) DPP‐4 inhibitor glycaemic control Hypoglycemia Metformin SGLT2 inhibitor type 2 diabetes |
| title | Efficacy and tolerability of initial triple combination therapy with metformin, dapagliflozin and saxagliptin compared with stepwise add‐on therapy in drug‐naïve patients with type 2 diabetes (TRIPLE‐AXEL study): A multicentre, randomized, 104‐week, open‐label, active‐controlled trial |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-13T21%3A32%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Efficacy%20and%20tolerability%20of%20initial%20triple%20combination%20therapy%20with%20metformin,%20dapagliflozin%20and%20saxagliptin%20compared%20with%20stepwise%20add%E2%80%90on%20therapy%20in%20drug%E2%80%90na%C3%AFve%20patients%20with%20type%202%20diabetes%20(TRIPLE%E2%80%90AXEL%20study):%20A%20multicentre,%20randomized,%20104%E2%80%90week,%20open%E2%80%90label,%20active%E2%80%90controlled%20trial&rft.jtitle=Diabetes,%20obesity%20&%20metabolism&rft.au=Kim,%20Nam%20Hoon&rft.date=2024-09&rft.volume=26&rft.issue=9&rft.spage=3642&rft.epage=3652&rft.pages=3642-3652&rft.issn=1462-8902&rft.eissn=1463-1326&rft_id=info:doi/10.1111/dom.15705&rft_dat=%3Cproquest_cross%3E3087919161%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c2785-8d6d13994c03ea6bf282ca4637bc0730359727451601a9124edf7ad31b9716163%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=3087919161&rft_id=info:pmid/38853720&rfr_iscdi=true |