BackgroundPreventable drug-related hospital admissions can be associated with drugs used in diabetes and the benefits of strict diabetes control may not outweigh the risks, especially in older populations. The aim of this study was to look for evidence on risks and benefits of DPP-4 inhibitors in older adults and to use this evidence to develop recommendations for the electronic decision support tool of the PRIMA-eDS project.MethodsSystematic review using a staged approach which searches for systematic reviews and meta-analyses first, then individual studies only if prior searches were inconclusive. The target population were older people (≥65 years old) with type 2 diabetes. We included studies reporting on the efficacy and/or safety of DPP-4 inhibitors for the management of type 2 diabetes. Studies were included irrespective of DPP-4 inhibitors prescribed as monotherapy or in combination with any other drug for the treatment of type 2 diabetes. The target intervention was DPP-4 inhibitors compared to placebo, no treatment, other drugs to treat type 2 diabetes or a non-pharmacological intervention.ResultsThirty studies (reported in 33 publications) were included: 1 meta-analysis, 17 intervention studies and 12 observational studies. Sixteen studies were focused on older adults and 14 studies reported subgroup analyses in participants ≥65, ≥70, or ≥75 years. Comorbidities were reported by 26 studies and frailty or functional status by one study. There were conflicting findings regarding the effectiveness of DPP-4 inhibitors in older adults. In general, DPP-4 inhibitors showed similar or better safety than placebo and other antidiabetic drugs. However, these safety data are mainly based on short-term outcomes like hypoglycaemia in studies with HbA1c control levels recommended for younger people. One recommendation was developed advising clinicians to reconsider the use of DPP-4 inhibitors for the management of type 2 diabetes in older adults with HbA1c <8.5% because of scarce data on clinically relevant benefits of their use. Twenty-two of the included studies were funded by pharmaceutical companies and authored or co-authored by employees of the sponsor.ConclusionsOther than the surrogate endpoint of improved glycaemic control, data on clinically relevant benefits of DPP-4 inhibitors in the treatment of type 2 diabetes mellitus in older adults is scarce. DPP-4 inhibitors might have a lower risk of hypoglycaemia compared to other antidiabetic drugs but data show conflicting findings for long-term benefits. Further studies are needed that evaluate the risks and benefits of DPP-4 inhibitors for the management of type 2 diabetes mellitus in older adults, using clinically relevant outcomes and including representative samples of older adults with information on their frailty status and comorbidities. Studies are also needed that are independent of pharmaceutical company involvement.

BackgroundThiazides are commonly prescribed to older people for the management of hypertension. The objective of this study was to identify the evidence on the risks and benefits of their use among adults aged ≥65 years and to develop recommendations to reduce potentially inappropriate use.MethodsSystematic review (SR) of the literature covering six databases. We applied a staged search approach, where each search was undertaken only if the previous one did not yield high quality results. Searches 1 and 2 identified relevant SRs and meta-analyses published up to December 2015 from all databases. Search 3 identified additional individual interventional studies (IS) and observational studies (OS) not identified by the preceding searches. We included all studies evaluating the effect of thiazides on patient-relevant outcomes in the management of hypertension with a sufficient number of participants aged ≥65 years or a subgroup analysis based on age. Two independent reviewers extracted data and carried out quality appraisal. Recommendations were developed using the GRADE methodology.ResultsSearches 1 to 3 were performed. We included 34 articles reporting on 12 IS and 4 OS. Mean ages ranged from 59 to 83.8 years. Four studies had performed a subgroup analysis by age. Information on comorbidity, polypharmacy and frailty of the participants was scarce or not available. The IS compared thiazides to placebo or other antihypertensive drugs and evaluated cardiovascular endpoints or all-cause-mortality as primary outcomes. The OS investigated the association between thiazide use and the risk of gout, fractures and adverse effects. Our results suggest that thiazides are efficacious in preventing cardiovascular events for this population group. Low-dose regimens of thiazides may be safer than high-dose (low quality of evidence), and a history of gout may increase the risk of adverse events (low quality of evidence). Three recommendations were developed.ConclusionsThe use of low dose treatment with thiazides for the management of hypertension in adults aged 65 and older seems justified, unless a history of gout is present. The quality of the evidence is low and studies rarely describe characteristics of the participants such as polypharmacy and frailty. Further good quality studies are needed.

BackgroundThe benefit from a blood pressure lowering therapy with beta blockers may not outweigh its risks, especially in older populations. The aim of this study was to look for evidence on risks and benefits of beta blockers in older adults and to use this evidence to develop recommendations for the electronic decision support tool of the PRIMA-eDS project.MethodsSystematic review of the literature using a stage approach with searches for systematic reviews and meta-analyses first, and individual studies only if the previous searches are inconclusive. The target population were older adults (≥65 years old) with hypertension. We included studies reporting on the effectiveness and/or safety of beta blockers on clinically relevant endpoints (e.g. mortality, cardiovascular events, and stroke) in the management of hypertension. The recommendations were developed according to the GRADE methodology.ResultsFifteen studies were included, comprising one meta-analysis, four randomized controlled trials, six secondary analyses of randomized controlled trials and four observational studies. Seven studies involved only older adults and eight studies reported subgroup analyses by age. With regard to a composite endpoint (death, stroke or myocardial infarction) beta blockers were associated with a higher risk of events then were other antihypertensive agents. Further, beta blockers showed no benefit compared to other antihypertensive agents or placebo regarding mortality. They appear to be less effective than other antihypertensive agents in reducing cardiovascular events. Contradictory results were found regarding the effect of beta blockers on stroke. None of the studies explored the effect on quality of life, hospitalisation, functional impairment/status, safety endpoints or renal failure.ConclusionThe quality of current evidence to interpret the benefits of beta blockers in hypertension is rather weak. It cannot be recommended to use beta blockers in older adults as first line agent for hypertension.

BackgroundMetformin is usually prescribed as first line therapy for type 2 diabetes mellitus (DM2). However, the benefits and risks of metformin may be different for older people. This systematic review examined the available evidence on the safety and efficacy of metformin in the management of DM2 in older adults. The findings were used to develop recommendations for the electronic decision support tool of the European project PRIMA-eDS.MethodsThe systematic review followed a staged approach, initially searching for systematic reviews and meta-analyses first, and then individual studies when prior searches were inconclusive. The target population was older people (≥65 years old) with DM2. Studies were included if they reported safety or efficacy outcomes with metformin (alone or in combination) for the management of DM2 compared to placebo, usual or no treatment, or other antidiabetics. Using the evidence identified, recommendations were developed using GRADE methodology.ResultsFifteen studies were included (4 intervention and 11 observational studies). In ten studies at least 80% of participants were 65 years or older and 5 studies reported subgroup analyses by age. Comorbidities were reported by 9 studies, cognitive status was reported by 4 studies and functional status by 1 study. In general, metformin showed similar or better safety and efficacy than other specific or non-specific active treatments. However, these findings were mainly based on retrospective observational studies. Four recommendations were developed suggesting to discontinue the use of metformin for the management of DM2 in older adults with risk factors such as age > 80, gastrointestinal complaints during the last year and/or GFR ≤60 ml/min.ConclusionsOn the evidence available, the safety and efficacy profiles of metformin appear to be better, and certainly no worse, than other treatments for the management of DM2 in older adults. However, the quality and quantity of the evidence is low, with scarce data on adverse events such as gastrointestinal complaints or renal failure. Further studies are needed to more reliably assess the benefits and risks of metformin in very old (>80), cognitively and functionally impaired older people.

BackgroundThe benefit from a blood pressure lowering therapy with beta blockers may not outweigh its risks, especially in older populations. The aim of this study was to look for evidence on risks and benefits of beta blockers in older adults and to use this evidence to develop recommendations for the electronic decision support tool of the PRIMA-eDS project.MethodsSystematic review of the literature using a stage approach with searches for systematic reviews and meta-analyses first, and individual studies only if the previous searches are inconclusive. The target population were older adults (≥65 years old) with hypertension. We included studies reporting on the effectiveness and/or safety of beta blockers on clinically relevant endpoints (e.g. mortality, cardiovascular events, and stroke) in the management of hypertension. The recommendations were developed according to the GRADE methodology.ResultsFifteen studies were included, comprising one meta-analysis, four randomized controlled trials, six secondary analyses of randomized controlled trials and four observational studies. Seven studies involved only older adults and eight studies reported subgroup analyses by age. With regard to a composite endpoint (death, stroke or myocardial infarction) beta blockers were associated with a higher risk of events then were other antihypertensive agents. Further, beta blockers showed no benefit compared to other antihypertensive agents or placebo regarding mortality. They appear to be less effective than other antihypertensive agents in reducing cardiovascular events. Contradictory results were found regarding the effect of beta blockers on stroke. None of the studies explored the effect on quality of life, hospitalisation, functional impairment/status, safety endpoints or renal failure.ConclusionThe quality of current evidence to interpret the benefits of beta blockers in hypertension is rather weak. It cannot be recommended to use beta blockers in older adults as first line agent for hypertension.

BackgroundThiazides are commonly prescribed to older people for the management of hypertension. The objective of this study was to identify the evidence on the risks and benefits of their use among adults aged ≥65 years and to develop recommendations to reduce potentially inappropriate use.MethodsSystematic review (SR) of the literature covering six databases. We applied a staged search approach, where each search was undertaken only if the previous one did not yield high quality results. Searches 1 and 2 identified relevant SRs and meta-analyses published up to December 2015 from all databases. Search 3 identified additional individual interventional studies (IS) and observational studies (OS) not identified by the preceding searches. We included all studies evaluating the effect of thiazides on patient-relevant outcomes in the management of hypertension with a sufficient number of participants aged ≥65 years or a subgroup analysis based on age. Two independent reviewers extracted data and carried out quality appraisal. Recommendations were developed using the GRADE methodology.ResultsSearches 1 to 3 were performed. We included 34 articles reporting on 12 IS and 4 OS. Mean ages ranged from 59 to 83.8 years. Four studies had performed a subgroup analysis by age. Information on comorbidity, polypharmacy and frailty of the participants was scarce or not available. The IS compared thiazides to placebo or other antihypertensive drugs and evaluated cardiovascular endpoints or all-cause-mortality as primary outcomes. The OS investigated the association between thiazide use and the risk of gout, fractures and adverse effects. Our results suggest that thiazides are efficacious in preventing cardiovascular events for this population group. Low-dose regimens of thiazides may be safer than high-dose (low quality of evidence), and a history of gout may increase the risk of adverse events (low quality of evidence). Three recommendations were developed.ConclusionsThe use of low dose treatment with thiazides for the management of hypertension in adults aged 65 and older seems justified, unless a history of gout is present. The quality of the evidence is low and studies rarely describe characteristics of the participants such as polypharmacy and frailty. Further good quality studies are needed.