Incretin‐based therapy and the risk of diabetic foot ulcers and related events
Aim To investigate the effect of dipeptidyl peptidase‐4 inhibitors (DPP4‐Is) and glucagon‐like peptide‐1 receptor agonists (GLP1‐RAs) on diabetic foot ulcer (DFU) and DFU‐related outcomes (lower limb amputation [LLA], DFU‐related hospitalization and mortality). Methods We performed a cohort study wi...
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| Veröffentlicht in: | Diabetes, obesity & metabolism obesity & metabolism, 2024-09, Vol.26 (9), p.3764-3780 |
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| creator | Werkman, Nikki C. C. Driessen, Johanna H. M. Klungel, Olaf H. Schaper, Nicolaas S. Souverein, Patrick C. Stehouwer, Coen D. A. Nielen, Johannes T. H. |
| description | Aim
To investigate the effect of dipeptidyl peptidase‐4 inhibitors (DPP4‐Is) and glucagon‐like peptide‐1 receptor agonists (GLP1‐RAs) on diabetic foot ulcer (DFU) and DFU‐related outcomes (lower limb amputation [LLA], DFU‐related hospitalization and mortality).
Methods
We performed a cohort study with data from the Clinical Practice Research Datalink Aurum database with linkage to hospital data. We included people with type 2 diabetes starting treatment with metformin. Then we propensity score matched new users of DPP4‐Is and sulphonylureas (N = 98 770), and new users of GLP1‐RAs and insulin (N = 25 422). Cox proportional hazards models estimated the hazard ratios (HRs) for the outcomes.
Results
We observed a lower risk of DFU with both DPP4‐I use versus sulphonylurea use (HR 0.88, 95% confidence interval [CI]: 0.79‐0.97) and GLP1‐RA use versus insulin use (HR 0.44, 95% CI: 0.32‐0.60) for short‐term exposure (≤ 400 days) and HR 0.74 (95% CI: 0.60‐0.92) for long‐term exposure (>400 days). Furthermore, the risks of hospitalization and mortality were lower with both DPP4‐I use and GLP1‐RA use. The risk of LLA was lower with GLP1‐RA use. The results remained consistent across several sensitivity analyses.
Conclusions
Incretin‐based therapy was associated with a lower risk of DFU and DFU‐related outcomes. This suggests benefits for the use of this treatment in people at risk of DFU. |
| doi_str_mv | 10.1111/dom.15721 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3074728457</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3074728457</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3131-72c44576bcbe9bf89f7b319dccac659b59da2a4d989d12f2e2f0563d585f0f963</originalsourceid><addsrcrecordid>eNp10LtOwzAUBmALgWgpDLwAisQCQ1pf4tgeUblVKioDzJHji0hJk2InoG48As_Ik2CSwoCEF5_h8--jH4BjBMconImuV2NEGUY7YIiSlMSI4HS3m3HMBcQDcOD9EkKYEM72wYBwQRFnbAjuZ5Vypimqz_ePXHqjo-bJOLneRLLq5sgV_jmqbaQLmQeoIlvXTdSWyjjfIWdK2YSH5tVUjT8Ee1aW3hxt7xF4vL56mN7G88XNbHoxjxVBBMUMqyShLM1VbkRuubAsJ0hopaRKqcip0BLLRAsuNMIWG2whTYmmnFpoRUpG4KzPXbv6pTW-yVaFV6YsZWXq1mcEsoRhHv4I9PQPXdatq8J2QXEmkMAMBnXeK-Vq752x2doVK-k2GYLZd81ZqDnrag72ZJvY5iujf-VPrwFMevBWlGbzf1J2ubjrI78AJaSG2g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3087919270</pqid></control><display><type>article</type><title>Incretin‐based therapy and the risk of diabetic foot ulcers and related events</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Werkman, Nikki C. C. ; Driessen, Johanna H. M. ; Klungel, Olaf H. ; Schaper, Nicolaas S. ; Souverein, Patrick C. ; Stehouwer, Coen D. A. ; Nielen, Johannes T. H.</creator><creatorcontrib>Werkman, Nikki C. C. ; Driessen, Johanna H. M. ; Klungel, Olaf H. ; Schaper, Nicolaas S. ; Souverein, Patrick C. ; Stehouwer, Coen D. A. ; Nielen, Johannes T. H.</creatorcontrib><description>Aim
To investigate the effect of dipeptidyl peptidase‐4 inhibitors (DPP4‐Is) and glucagon‐like peptide‐1 receptor agonists (GLP1‐RAs) on diabetic foot ulcer (DFU) and DFU‐related outcomes (lower limb amputation [LLA], DFU‐related hospitalization and mortality).
Methods
We performed a cohort study with data from the Clinical Practice Research Datalink Aurum database with linkage to hospital data. We included people with type 2 diabetes starting treatment with metformin. Then we propensity score matched new users of DPP4‐Is and sulphonylureas (N = 98 770), and new users of GLP1‐RAs and insulin (N = 25 422). Cox proportional hazards models estimated the hazard ratios (HRs) for the outcomes.
Results
We observed a lower risk of DFU with both DPP4‐I use versus sulphonylurea use (HR 0.88, 95% confidence interval [CI]: 0.79‐0.97) and GLP1‐RA use versus insulin use (HR 0.44, 95% CI: 0.32‐0.60) for short‐term exposure (≤ 400 days) and HR 0.74 (95% CI: 0.60‐0.92) for long‐term exposure (>400 days). Furthermore, the risks of hospitalization and mortality were lower with both DPP4‐I use and GLP1‐RA use. The risk of LLA was lower with GLP1‐RA use. The results remained consistent across several sensitivity analyses.
Conclusions
Incretin‐based therapy was associated with a lower risk of DFU and DFU‐related outcomes. This suggests benefits for the use of this treatment in people at risk of DFU.</description><identifier>ISSN: 1462-8902</identifier><identifier>ISSN: 1463-1326</identifier><identifier>EISSN: 1463-1326</identifier><identifier>DOI: 10.1111/dom.15721</identifier><identifier>PMID: 38951877</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Aged ; Amputation ; Amputation, Surgical - statistics & numerical data ; Cohort Studies ; cohort study ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - complications ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetic Foot - drug therapy ; Diabetic Foot - epidemiology ; diabetic foot ulcer ; Dipeptidyl-Peptidase IV Inhibitors - adverse effects ; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use ; DPP4‐Is ; Female ; Foot diseases ; GLP-1 receptor agonists ; GLP1‐RAs ; Glucagon ; Glucagon-Like Peptide-1 Receptor - agonists ; Hospitalization - statistics & numerical data ; Humans ; Hypoglycemic Agents - adverse effects ; Hypoglycemic Agents - therapeutic use ; incretins ; Incretins - adverse effects ; Incretins - therapeutic use ; Insulin ; Insulin - therapeutic use ; Male ; Metformin ; Metformin - adverse effects ; Metformin - therapeutic use ; Middle Aged ; Mortality ; Plantar ulcers ; Proportional Hazards Models ; Sensitivity analysis ; Sulfonylurea Compounds - adverse effects ; Sulfonylurea Compounds - therapeutic use ; type 2 diabetes</subject><ispartof>Diabetes, obesity & metabolism, 2024-09, Vol.26 (9), p.3764-3780</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-c3131-72c44576bcbe9bf89f7b319dccac659b59da2a4d989d12f2e2f0563d585f0f963</cites><orcidid>0000-0002-3633-2504 ; 0000-0002-3878-8302 ; 0000-0001-8752-3223</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fdom.15721$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fdom.15721$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38951877$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Werkman, Nikki C. C.</creatorcontrib><creatorcontrib>Driessen, Johanna H. M.</creatorcontrib><creatorcontrib>Klungel, Olaf H.</creatorcontrib><creatorcontrib>Schaper, Nicolaas S.</creatorcontrib><creatorcontrib>Souverein, Patrick C.</creatorcontrib><creatorcontrib>Stehouwer, Coen D. A.</creatorcontrib><creatorcontrib>Nielen, Johannes T. H.</creatorcontrib><title>Incretin‐based therapy and the risk of diabetic foot ulcers and related events</title><title>Diabetes, obesity & metabolism</title><addtitle>Diabetes Obes Metab</addtitle><description>Aim
To investigate the effect of dipeptidyl peptidase‐4 inhibitors (DPP4‐Is) and glucagon‐like peptide‐1 receptor agonists (GLP1‐RAs) on diabetic foot ulcer (DFU) and DFU‐related outcomes (lower limb amputation [LLA], DFU‐related hospitalization and mortality).
Methods
We performed a cohort study with data from the Clinical Practice Research Datalink Aurum database with linkage to hospital data. We included people with type 2 diabetes starting treatment with metformin. Then we propensity score matched new users of DPP4‐Is and sulphonylureas (N = 98 770), and new users of GLP1‐RAs and insulin (N = 25 422). Cox proportional hazards models estimated the hazard ratios (HRs) for the outcomes.
Results
We observed a lower risk of DFU with both DPP4‐I use versus sulphonylurea use (HR 0.88, 95% confidence interval [CI]: 0.79‐0.97) and GLP1‐RA use versus insulin use (HR 0.44, 95% CI: 0.32‐0.60) for short‐term exposure (≤ 400 days) and HR 0.74 (95% CI: 0.60‐0.92) for long‐term exposure (>400 days). Furthermore, the risks of hospitalization and mortality were lower with both DPP4‐I use and GLP1‐RA use. The risk of LLA was lower with GLP1‐RA use. The results remained consistent across several sensitivity analyses.
Conclusions
Incretin‐based therapy was associated with a lower risk of DFU and DFU‐related outcomes. This suggests benefits for the use of this treatment in people at risk of DFU.</description><subject>Aged</subject><subject>Amputation</subject><subject>Amputation, Surgical - statistics & numerical data</subject><subject>Cohort Studies</subject><subject>cohort study</subject><subject>Diabetes</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - complications</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetic Foot - drug therapy</subject><subject>Diabetic Foot - epidemiology</subject><subject>diabetic foot ulcer</subject><subject>Dipeptidyl-Peptidase IV Inhibitors - adverse effects</subject><subject>Dipeptidyl-Peptidase IV Inhibitors - therapeutic use</subject><subject>DPP4‐Is</subject><subject>Female</subject><subject>Foot diseases</subject><subject>GLP-1 receptor agonists</subject><subject>GLP1‐RAs</subject><subject>Glucagon</subject><subject>Glucagon-Like Peptide-1 Receptor - agonists</subject><subject>Hospitalization - statistics & numerical data</subject><subject>Humans</subject><subject>Hypoglycemic Agents - adverse effects</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>incretins</subject><subject>Incretins - adverse effects</subject><subject>Incretins - therapeutic use</subject><subject>Insulin</subject><subject>Insulin - therapeutic use</subject><subject>Male</subject><subject>Metformin</subject><subject>Metformin - adverse effects</subject><subject>Metformin - therapeutic use</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Plantar ulcers</subject><subject>Proportional Hazards Models</subject><subject>Sensitivity analysis</subject><subject>Sulfonylurea Compounds - adverse effects</subject><subject>Sulfonylurea Compounds - therapeutic use</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><sourceid>EIF</sourceid><recordid>eNp10LtOwzAUBmALgWgpDLwAisQCQ1pf4tgeUblVKioDzJHji0hJk2InoG48As_Ik2CSwoCEF5_h8--jH4BjBMconImuV2NEGUY7YIiSlMSI4HS3m3HMBcQDcOD9EkKYEM72wYBwQRFnbAjuZ5Vypimqz_ePXHqjo-bJOLneRLLq5sgV_jmqbaQLmQeoIlvXTdSWyjjfIWdK2YSH5tVUjT8Ee1aW3hxt7xF4vL56mN7G88XNbHoxjxVBBMUMqyShLM1VbkRuubAsJ0hopaRKqcip0BLLRAsuNMIWG2whTYmmnFpoRUpG4KzPXbv6pTW-yVaFV6YsZWXq1mcEsoRhHv4I9PQPXdatq8J2QXEmkMAMBnXeK-Vq752x2doVK-k2GYLZd81ZqDnrag72ZJvY5iujf-VPrwFMevBWlGbzf1J2ubjrI78AJaSG2g</recordid><startdate>202409</startdate><enddate>202409</enddate><creator>Werkman, Nikki C. C.</creator><creator>Driessen, Johanna H. M.</creator><creator>Klungel, Olaf H.</creator><creator>Schaper, Nicolaas S.</creator><creator>Souverein, Patrick C.</creator><creator>Stehouwer, Coen D. A.</creator><creator>Nielen, Johannes T. H.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</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/0000-0002-3633-2504</orcidid><orcidid>https://orcid.org/0000-0002-3878-8302</orcidid><orcidid>https://orcid.org/0000-0001-8752-3223</orcidid></search><sort><creationdate>202409</creationdate><title>Incretin‐based therapy and the risk of diabetic foot ulcers and related events</title><author>Werkman, Nikki C. C. ; Driessen, Johanna H. M. ; Klungel, Olaf H. ; Schaper, Nicolaas S. ; Souverein, Patrick C. ; Stehouwer, Coen D. A. ; Nielen, Johannes T. H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3131-72c44576bcbe9bf89f7b319dccac659b59da2a4d989d12f2e2f0563d585f0f963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Aged</topic><topic>Amputation</topic><topic>Amputation, Surgical - statistics & numerical data</topic><topic>Cohort Studies</topic><topic>cohort study</topic><topic>Diabetes</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2 - complications</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetic Foot - drug therapy</topic><topic>Diabetic Foot - epidemiology</topic><topic>diabetic foot ulcer</topic><topic>Dipeptidyl-Peptidase IV Inhibitors - adverse effects</topic><topic>Dipeptidyl-Peptidase IV Inhibitors - therapeutic use</topic><topic>DPP4‐Is</topic><topic>Female</topic><topic>Foot diseases</topic><topic>GLP-1 receptor agonists</topic><topic>GLP1‐RAs</topic><topic>Glucagon</topic><topic>Glucagon-Like Peptide-1 Receptor - agonists</topic><topic>Hospitalization - statistics & numerical data</topic><topic>Humans</topic><topic>Hypoglycemic Agents - adverse effects</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>incretins</topic><topic>Incretins - adverse effects</topic><topic>Incretins - therapeutic use</topic><topic>Insulin</topic><topic>Insulin - therapeutic use</topic><topic>Male</topic><topic>Metformin</topic><topic>Metformin - adverse effects</topic><topic>Metformin - therapeutic use</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Plantar ulcers</topic><topic>Proportional Hazards Models</topic><topic>Sensitivity analysis</topic><topic>Sulfonylurea Compounds - adverse effects</topic><topic>Sulfonylurea Compounds - therapeutic use</topic><topic>type 2 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Werkman, Nikki C. C.</creatorcontrib><creatorcontrib>Driessen, Johanna H. M.</creatorcontrib><creatorcontrib>Klungel, Olaf H.</creatorcontrib><creatorcontrib>Schaper, Nicolaas S.</creatorcontrib><creatorcontrib>Souverein, Patrick C.</creatorcontrib><creatorcontrib>Stehouwer, Coen D. A.</creatorcontrib><creatorcontrib>Nielen, Johannes T. H.</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</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>Werkman, Nikki C. C.</au><au>Driessen, Johanna H. M.</au><au>Klungel, Olaf H.</au><au>Schaper, Nicolaas S.</au><au>Souverein, Patrick C.</au><au>Stehouwer, Coen D. A.</au><au>Nielen, Johannes T. H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Incretin‐based therapy and the risk of diabetic foot ulcers and related events</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>3764</spage><epage>3780</epage><pages>3764-3780</pages><issn>1462-8902</issn><issn>1463-1326</issn><eissn>1463-1326</eissn><abstract>Aim
To investigate the effect of dipeptidyl peptidase‐4 inhibitors (DPP4‐Is) and glucagon‐like peptide‐1 receptor agonists (GLP1‐RAs) on diabetic foot ulcer (DFU) and DFU‐related outcomes (lower limb amputation [LLA], DFU‐related hospitalization and mortality).
Methods
We performed a cohort study with data from the Clinical Practice Research Datalink Aurum database with linkage to hospital data. We included people with type 2 diabetes starting treatment with metformin. Then we propensity score matched new users of DPP4‐Is and sulphonylureas (N = 98 770), and new users of GLP1‐RAs and insulin (N = 25 422). Cox proportional hazards models estimated the hazard ratios (HRs) for the outcomes.
Results
We observed a lower risk of DFU with both DPP4‐I use versus sulphonylurea use (HR 0.88, 95% confidence interval [CI]: 0.79‐0.97) and GLP1‐RA use versus insulin use (HR 0.44, 95% CI: 0.32‐0.60) for short‐term exposure (≤ 400 days) and HR 0.74 (95% CI: 0.60‐0.92) for long‐term exposure (>400 days). Furthermore, the risks of hospitalization and mortality were lower with both DPP4‐I use and GLP1‐RA use. The risk of LLA was lower with GLP1‐RA use. The results remained consistent across several sensitivity analyses.
Conclusions
Incretin‐based therapy was associated with a lower risk of DFU and DFU‐related outcomes. This suggests benefits for the use of this treatment in people at risk of DFU.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>38951877</pmid><doi>10.1111/dom.15721</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0002-3633-2504</orcidid><orcidid>https://orcid.org/0000-0002-3878-8302</orcidid><orcidid>https://orcid.org/0000-0001-8752-3223</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Amputation Amputation, Surgical - statistics & numerical data Cohort Studies cohort study Diabetes Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - drug therapy Diabetic Foot - drug therapy Diabetic Foot - epidemiology diabetic foot ulcer Dipeptidyl-Peptidase IV Inhibitors - adverse effects Dipeptidyl-Peptidase IV Inhibitors - therapeutic use DPP4‐Is Female Foot diseases GLP-1 receptor agonists GLP1‐RAs Glucagon Glucagon-Like Peptide-1 Receptor - agonists Hospitalization - statistics & numerical data Humans Hypoglycemic Agents - adverse effects Hypoglycemic Agents - therapeutic use incretins Incretins - adverse effects Incretins - therapeutic use Insulin Insulin - therapeutic use Male Metformin Metformin - adverse effects Metformin - therapeutic use Middle Aged Mortality Plantar ulcers Proportional Hazards Models Sensitivity analysis Sulfonylurea Compounds - adverse effects Sulfonylurea Compounds - therapeutic use type 2 diabetes |
| title | Incretin‐based therapy and the risk of diabetic foot ulcers and related events |
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