2024+ACP临床指南：成人2型糖尿病的新药物治疗.pdf

Newer Pharmacologic Treatments in Adults With Type 2 Diabetes:A Clinical Guideline From the American College of PhysiciansAmir Qaseem,MD,PhD,MHA;Adam J.Obley,MD;Tatyana Shamliyan,MD,MS;Lauri A.Hicks,DO;Curtis S.Harrod,PhD,MPH;and Carolyn J.Crandall,MD,MS;for the Clinical Guidelines Committee of the American College of Physicians*Description:The American College of Physicians(ACP)developed this clinical guideline to update recommen-dations on newer pharmacologic treatments of type 2diabetes.This clinical guideline is based on the bestavailable evidence for effectiveness,comparative ben-efits and harms,consideration of patients values andpreferences,and costs.Methods:This clinical guideline is based on a system-atic review of the effectiveness and harms of newerpharmacologic treatments of type 2 diabetes,includingglucagon-like peptide-1(GLP-1)agonists,a GLP-1 ago-nist and glucose-dependent insulinotropic polypeptideagonist,sodiumglucose cotransporter-2(SGLT-2)inhibitors,dipeptidyl peptidase-4(DPP-4)inhibitors,and long-acting insulins,used either as monotherapyor in combination with other medications.The ClinicalGuidelines Committee prioritized the following out-comes,which were evaluated using the GRADE(Grading of Recommendations Assessment,Develop-ment and Evaluation)approach:all-cause mortality,major adverse cardiovascular events,myocardial in-farction,stroke,hospitalization for congestive heartfailure,progression of chronic kidney disease,seriousadverse events,and severe hypoglycemia.Weightloss,as measured by percentage of participants whoachieved at least 10%total body weight loss,was aprioritized outcome,but data were insufficient for net-work meta-analysis and were not rated with GRADE.Audience and Patient Population:The audience forthis clinical guideline is physicians and other clini-cians.The population is nonpregnant adults with type2 diabetes.Recommendation 1:ACP recommends adding asodiumglucose cotransporter-2(SGLT-2)inhibi-tor or glucagon-like peptide-1(GLP-1)agonist to met-formin and lifestyle modifications in adults with type 2diabetes and inadequate glycemic control(strongrecommendation;high-certainty evidence).?Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality,major adverse cardiovascular events,progression of chronic kidney disease,and hospitali-zation due to congestive heart failure.?Use a GLP-1 agonist to reduce the risk for all-causemortality,major adverse cardiovascular events,andstroke.Recommendation 2:ACP recommends against add-ing a dipeptidyl peptidase-4(DPP-4)inhibitor to met-formin and lifestyle modifications in adults with type 2diabetes and inadequate glycemic control to reducemorbidity and all-cause mortality(strong recommen-dation;high-certainty evidence).Ann Intern Med.doi:10.7326/M23-2788Annals.orgFor author,article,and disclosure information,see end of text.This article was published at Annals.org on 19 April 2024.The age-adjusted prevalence of type 2 diabetes inadults is 14.8%in the United States(1)and 10.5%globally(2).The age-adjusted incidence of type 2 dia-betes in U.S.adults is 5.8 per 1000 persons;however,an estimated 23%of the U.S.adults with type 2 diabe-tes are undiagnosed(3).Type 2 diabetes is associated with higher risk formortality and morbidity,greater health care use,andgreater costs when adultswithdiabetes are comparedwith those without diabetes(4).The economic burdenof type 2 diabetes in the United States is substantial,with an annual estimated cost of$327 billion,includ-ing$237 billion in direct medical costs and$90 billionin reduced productivity(5).*This article,authored by Amir Qaseem,MD,PhD,MHA;Adam J.Obley,MD;Tatyana Shamliyan,MD,MS;Lauri A.Hicks,DO;Curtis S.Harrod,PhD,MPH;andCarolyn J.Crandall,MD,MS,was developed for the Clinical Guidelines Committee of the American College of Physicians.Individuals who served on theClinical Guidelines Committee from initiation of the project until its approval were Carolyn J.Crandall,MD,MS(Chair);Lauri A.Hicks,DO(Vice Chair);Timothy J.Wilt,MD,MPH(Immediate Past Chair);Ethan M.Balk,MD,MPH;Thomas G.Cooney,MD;J.Thomas Cross Jr.,MD,MPH;Nick Fitterman,MD;Jennifer S.Lin,MD,MCR;Michael Maroto,JD,MBA;Matthew C.Miller,MD;Adam J.Obley,MD;Douglas K.Owens,MD,MS;Paul Shekelle,MD,PhD,MPH;Jeffrey A.Tice,MD;and Janice E.Tufte.ACP staff were Kate Carroll,MPH;Itziar Etxeandia-Ikobaltzeta,PhD,PharmD;Curtis S.Harrod,PhD,MPH;Amir Qaseem,MD,PhD,MHA;Tatyana Shamliyan,MD,MS;and Jennifer Yost,PhD,RN.Approved by the ACP Board of Regents on 4 November 2023.Author.Nonauthor contributor.Nonphysician public representative.See also:Related articlesEditorial commentWeb-OnlySupplementVisual Clinical GuidelineAnnals.orgAnnals of Internal Medicine 2024 American College of Physicians 1CLINICALGUIDELINEDownloaded from https:/annals.org by Guangdong University of Technology on 04/19/2024.Type 2 diabetes disproportionately affects adultswith obesity and racial and ethnic minorities(6).Forexample,the age-adjusted prevalence of type 2 diabe-tes is higher in Black(19%)and Hispanic(21%)adultsthan in White adults(12%)(7).People with type 2 dia-betes and social risk factors are more likely to die pre-maturely and to have health-related complications,poor access to high-quality health care,and difficultywith adherence to treatments than people with type 2diabetes who do not have adverse social risk factors(815).In the United States,the excess risk for prema-ture deaths attributed to type 2 diabetes decreasedbetween 1997 and 2011 among Hispanic and Whiteadults,but not among Black adults(16).Access tohigh-quality health care in people with type 2 diabe-tes differs by race and ethnicity even after adjustmentfor socioeconomic,lifestyle,and health factors(17).Itis important to note that race and ethnicity are socialconstructs rather than biological risk factors.Differencesin risk for diabetes and outcomes in people with diabe-tes may be mediated by such factors as social determi-nantsofhealth.Majortreatmentgoalsfor patientswithtype2diabe-tes include adequate glycemic control and primary andsecondary prevention of atherosclerotic cardiovascularand kidney diseases,which account for nearly half of alldeaths among adults with type 2 diabetes(18).Despitemultiple treatment options,16%of adults with type 2diabetes have inadequate glycemic control,with hemo-globin A1c(HbA1c)levels of 9%or higher(7).Inadequateglycemic control is more prevalent among Black(24%)and Hispanic(29%)adults than among White adults(9%)with type 2 diabetes(7).In 2017,the American College of Physicians(ACP)published a clinical guideline on oral pharmacologictreatments of type 2 diabetes focused on glycemiccontrol(19).The ACP Clinical Guidelines Committee(CGC)recommended that clinicians prescribe met-formin,in addition to lifestyle treatments,when phar-macologic therapy is needed to improve glycemiccontrol in adults with type 2 diabetes(19).SCOPE ANDPURPOSEThis ACP clinical guideline is an update to the 2017version(19)with evidence about the effectiveness andharms of newer pharmacologic treatments to reducetheriskforall-causemortality,cardiovascular morbidity,and progression of chronic kidney disease(CKD)inadults with type 2 diabetes.In addition toincorporatingnetwork meta-analyses(NMAs),this clinical guidelineadds key questions on patient values and preferencesand economic evidence.Newer pharmacologic treatments include glucagon-like peptide-1(GLP-1)agonists(dulaglutide,exenatide,liraglutide,lixisenatide,and semaglutide),a GLP-1 ago-nist and glucose-dependent insulinotropic polypeptideagonist(tirzepatide),sodiumglucose cotransporter-2(SGLT-2)inhibitors(canagliflozin,dapagliflozin,empa-gliflozin,and ertugliflozin),dipeptidyl peptidase-4(DPP-4)inhibitors(alogliptin,linagliptin,saxagliptin,and sita-gliptin),and long-acting insulins(insulin glargine andinsulin degludec).The CGC did not consider studiesofhospitalizedadultswithtype2diabetes;type2diabe-tes management in adults with acute comorbid condi-tions,including acute stroke and myocardial infarction(MI);or adults with type 2 diabetes undergoing sur-gery or active cancer treatment.POPULATIONThe patient population is nonpregnant adults withtype 2 diabetes.INTENDEDAUDIENCEThe intended audience is physicians and otherclinicians caring for adults with type 2 diabetes.GUIDELINEDEVELOPMENTPROCESSThe CGC developed this clinical guideline accord-ing to ACPs guideline development methods(20)and its policy on disclosure of interests and manage-ment of conflicts of interest(21).The CGC used theEvidence-to-Decision framework when reportingevidence(Supplement Tables 1 to 5,available atAnnals.org)and rated the recommendations usingthe GRADE(Grading of Recommendations Assessment,Development and Evaluation)approach(22)(Figure 1).The Appendix(available at Annals.org)lists the keyquestions for the supporting systematic reviews(Appendix Table 1,available at Annals.org),describesthe selection and definition of critical and importantclinical outcomes,and details the methods used for theclinical guideline and systematic reviews.SupplementTables 1 to 5 incorporate evidence from systematicreviews alongside interpretation and judgements madeby the CGC,which are briefly summarized in Figures 2and 3.ACP completes a Guidelines InternationalNetwork Guideline Standards(23)reporting formfor each clinical guideline it publishes,which can befound in the Networks International Guidelines Libraryor on ACPs website(www.acponline.org/clinical-information/guidelines/guideline-process).SYSTEMATICREVIEW OFBENEFITS ANDHARMSANDSUMMARY OF THEEVIDENCEThis clinical guideline is based on an accompany-ing systematic review and NMA of randomized con-trolled trials(RCTs)with at least 12 months of treatmentand follow-up that examined the benefits and harms ofnewer pharmacologic treatments in adults with type 2diabetes(24).Thesystematicreviewand NMAwas com-pleted by the ACP Center for Evidence Reviews atMinnesota and funded by ACP.CLINICALGUIDELINEACP Guideline on Newer Pharmacologic Treatments in Adults With Diabetes2 Annals of Internal MedicineAnnals.orgDownloaded from https:/annals.org by Guangdong University of Technology on 04/19/2024.Although the systematic review was not limited toadd-on therapy in which a newer pharmacologic treat-ment of type 2 diabetes was added to usual care inadults with inadequate glycemic control,that is howmost included studies were designed.The most com-mon usual care medication in the included trials wasmetformin.In assessing the applicability of the evi-dence,the CGC considered glycemic control and life-style modifications directed by study investigatorsand physicians,prior treatments,risk for cardiovascu-lar diseases(CVDs),presence of CKD,and comorbidconditions at baseline.OUTCOMES OFINTERESTBenefits and HarmsThe CGC,CGC Public Panel,and members of thetopic expert panel for the systematic review inde-pendently rated the importance of clinical outcomesas“critical,”“important,”or“less important”for decisionmaking(Appendix Table 2,available at Annals.org).The CGC prioritized the following outcomes for deci-sionmaking:all-causemortality,congestiveheartfailure(CHF)requiring hospitalization,major adverse cardio-vascular events(MACE;generally defined as theoccurrence of cardiovascular death,a nonfatal MI,or a nonfatal stroke),MI alone,progression of CKD,serious adverse events(SAEs),severe hypoglyce-mia,stroke alone,and weight change(as measuredby achieving 10%total body weight loss).However,the Center for Evidence Reviews did not appraise thecertainty of evidence for total body weight loss of 10%or more because data were heterogeneous and insuf-ficient to include in the NMA.Glycemic control wasnot a prioritized outcome because all eligible medi-cations have been shown to improve this surrogatemeasure.Public and Patient Values and PreferencesThe CGC assessed the evidence in the systematicreview about values and preferences for newer phar-macologic treatments in adults with type 2 diabetes(Supplement Table 6,available at Annals.org).Evidenceabout public and patient values and preferenceswas identified through 2 sources,the accompanyingreview of research evidence conducted by the Centerfor Evidence Reviews and consultation with the CGCPublic Panel.The CGC Public Panel was engaged inrating the importance of clinical outcomes,as well asproviding their views on the findings from the system-atic review about the benefits and harms of treatmentoptions.In addition,the CGC Public Panel providedfeedback on treatment selection preferences andguideline recommendations.CostsThe CGC considered costs and the economic bur-den of care when assessing the value of the treat-ments.The Center for Evidence Reviews completed aseparate systematic review(funded by ACP)(25)on theeconomic value of treatments based on willingness-to-pay thresholds for incremental cost-effectiveness ratioper quality-adjusted life-year gained reported in high-quality cost-effectiveness analyses applicable to theUnited States(26,27).Average annual Medicarespending per beneficiary for type 2 diabetes medi-cations is reported in Supplement Tables 7 and 8(available at Annals.org).A summary of findings forthe systematic review on cost-effectiveness analysesis in Supplement Table 9(available at Annals.org).RECOMMENDATIONSA visual clinical guideline for this topic displayinga visual summary of the recommendations,rationales,and clinical considerations,alongside an interactivedata visualization,is available at Annals.org(28).Figure 1.Grading the certainty of evidence and strength of recommendations in ACP clinical guidelines using GRADE.HighModerateLowStrengthBalance of Benefits and HarmsApplicable Patient PopulationPolicy ImplicationsStrong(ACP recommends)Confidence that the benefits clearlyoutweigh risks and burden or viceversa.Applies to most patientsin most circumstances.Benefits probably outweigh the risksand burden,or vice versa,but thereis appreciable uncertainty.Applies to many patients butmay differ depending oncircumstances or patientsvalues and preferences.Policymaking will require substantial debates and involvementof many stakeholders.Policies are also more likely to varybetween regions.Quality indicators would have to focus on thefact that adequate deliberation about the management optionshas taken place.Grading Strength of RecommendationsGrading Certainty of EvidenceConfident that the true effect lies close to the estimate of the effect(the intervention“results in”the effect).Moderately confident in the effect estimate:The true effect is likely to be close to the estimate of the effect,but there is a sizeablepossibility that it is substantially different(the intervention“probably results in”the effect).Confidence in the effect estimate is limited:The true effect may be substantially different from the estimate of the effect(theintervention“may result in”the effect).Only strong recommendations could be considered as qualityindicators to guide the development of accountability,reporting,and payment programs