6.0.0.0 PHAR­MA­CO­LOG­IC THER­A­PY

Rec­om­men­da­tions

12.11 In older adults at in­creased risk of hy­po­glycemia, med­i­ca­tion class­es with low risk of hy­po­glycemia are pre­ferred. B

12.12 Overtreat­ment of di­a­betes is com­mon in older adults and should be avoid­ed. B

12.13 Dein­ten­sification (or sim­plification) of com­plex reg­i­mens is rec­om­mend­ed to re­duce the risk of hy­po­glycemia, if it can be achieved with­in the in­di­vid­u­al­ized A1C tar­get. B

Fig. 12.1

Fig. 12.1 —Al­go­rithm to sim­pli­fy in­sulin reg­i­men for older pa­tients with type 2 di­a­betes. eGFR, es­ti­mat­ed glomeru­lar filtra­tion rate.
*Basal in­sulins: glargine U-100 and U-300, de­temir, degludec, and human NPH.
**See Table 12.1. ¥Meal­time in­sulins: short-‍act­ing (reg­u­lar human in­sulin) or rap­i­dact­ing (lispro, as­part, and gluli­sine).

§Pre­mixed in­sulins: 70/30, 75/25, and 50/50 prod­ucts. Adapt­ed with per­mis­sion from Mun­shi and col­leagues (39,55,56).

Spe­cial care is re­quired in pre­scrib­ing and mon­i­tor­ing phar­ma­co­log­ic ther­a­pies in older adults (33). See Fig. 9.1 for gen­er­al rec­om­men­da­tions re­gard­ing antihy­per­glycemia treat­ment for adults with type 2 di­a­betes and Table 9.1 for pa­tient-‍ and drug-‍specific fac­tors to con­sid­er when se­lect­ing antihy­per­glycemia agents. Cost may be an im­por­tant con­sid­eration, es­pe­cial­ly as older adults tend to be on many med­i­ca­tions. See Ta­bles 9.2 and 9.3 for me­di­an month­ly cost of nonin­sulin glu­cose-‍low­er­ing agents and in­sulin in the U.S., re­spec­tive­ly. It is im­por­tant to match com­plexity of the treat­ment reg­i­men to the self-‍man­age­ment abil­i­ty of an older pa­tient. Many older adults with di­a­betes strug­gle to main­tain the fre­quent blood glu­cose test­ing and in­sulin in­jec­tion reg­i­mens they pre­vi­ous­ly fol­lowed, per­haps for many decades, as they de­vel­op med­i­cal con­di­tions that may im­pair their abil­i­ty to fol­low their reg­i­men safe­ly. In­di­vid­u­al­ized glycemic goals should be es­tab­lished (Fig. 6.1) and pe­ri­od­i­cal­ly ad­just­ed based on co­ex­ist­ing chron­ic ill­ness­es, cog­ni­tive func­tion, and func­tion­al sta­tus (2). Tight glycemic con­trol in older adults with mul­ti­ple med­i­cal con­di­tions is con­sid­ered overtreat­ment and is as­so­ci­at­ed with an in­creased risk of hy­po­glycemia; un­for­tu­nate­ly, overtreat­ment is com­mon in clin­i­cal prac­tice (34-38). Dein­ten­sification of reg­i­mens in pa­tients tak­ing nonin­sulin glu­cose-‍low­er­ing med­i­ca­tions can be achieved by ei­ther low­er­ing the dose or dis­con­tin­u­ing some med­i­ca­tions, so long as the in­di­vid­u­al­ized A1C tar­get is main­tained. When pa­tients are found to have an in­sulin reg­i­men with com­plexity be­yond their self-‍man­age­ment abil­i­ties, low­er­ing the dose of in­sulin may not be ad­e­quate. Sim­plification of the in­sulin reg­i­men to match an in­di­vid­u­al’s self-‍man­age­ment abil­i­ties in these sit­u­a­tions has been shown to re­duce hy­po­glycemia and dis­ease-‍re­lat­ed dis­tress with­out wors­en­ing glycemic con­trol (39-41). Fig­ure 12.1 de­picts an al­go­rithm that can be used to sim­pli­fy the in­sulin reg­i­men (39). Table 12.2 pro­vides ex­am­ples of and ra­tio­nale for sit­u­a­tions where dein­ten­sification and/‍or in­sulin reg­i­men sim­plification may be ap­pro­pri­ate in older adults.

Met­formin

Met­formin is the first-‍line agent for older adults with type 2 di­a­betes. Re­cent stud­ies have in­di­cat­ed that it may be used safe­ly in pa­tients with es­ti­mat­ed glomeru­lar filtra­tion rate ≥30 mL/‍min/‍1.73 m2 (42). How­ev­er, it is contrain­di­cat­ed in pa­tients with ad­vanced renal insufficien­cy and should be used with cau­tion in pa­tients with im­paired hep­at­ic func­tion or con­ges­tive heart fail­ure due to the in­creased risk of lac­tic aci­do­sis. Met­formin may be tem­porar­i­ly dis­con­tin­ued be­fore pro­ce­dures, dur­ing hos­pi­tal­iza­tions, and when acute ill­ness may com­pro­mise renal or liver func­tion.

Thi­a­zo­lidine­diones

Thi­a­zo­lidine­diones, if used at all, should be used very cau­tious­ly in those with, or at risk for, con­ges­tive heart fail­ure and those at risk for falls or frac­tures.

In­sulin Sec­re­t­a­gogues

Sul­fony­lureas and other in­sulin sec­re­t­a­gogues are as­so­ci­at­ed with hy­po­glycemia and should be used with cau­tion. If used, shorter-du­ra­tion sul­fony­lureas, such as glip­izide, are pre­ferred. Gly­buride is a longer-‍du­ra­tion sul­fony­lurea and contrain­di­cat­ed in older adults (43).

In­cretin-‍Based Ther­a­pies

Oral dipep­tidyl pep­ti­dase 4 (DPP-4) in­hibitors have few side ef­fects and min­i­mal hy­po­glycemia, but their costs may be a bar­ri­er to some older pa­tients. DPP-4 in­hibitors do not in­crease major ad­verse cardiovas­cu­lar out­comes (44).

Glucagon-‍like pep­tide 1 (GLP-1) re­cep­tor ag­o­nists are in­jectable agents, which re­quire vi­su­al, motor, and cog­ni­tive skills for ap­pro­pri­ate ad­min­is­tra­tion. They may be as­so­ci­at­ed with nau­sea, vom­it­ing, and di­ar­rhea. Also, weight loss with GLP-1 re­cep­tor ag­o­nists may not be de­sir­able in some older pa­tients, par­tic­u­lar­ly those with cachex­ia. In pa­tients with es­tab­lished atheroscle­rot­ic cardiovas­cu­lar dis­ease, GLP-1 re­cep­tor ag­o­nists have shown cardiovas­cu­lar benefits (44).

Table 12.2—Con­sid­erations for treat­ment reg­i­men sim­plification and dein­ten­sification/depre­scrib­ing in older adults with di­a­betes (39,55)

Table 12.2

Treat­ment reg­i­men sim­plification refers to chang­ing strat­e­gy to de­crease the com­plexity of a med­i­ca­tion reg­i­men, e.g., fewer ad­min­is­tra­tion times, fewer finger­stick read­ings, de­creas­ing the need for cal­cu­la­tions (such as slid­ing scale in­sulin cal­cu­la­tions or in­sulin-carbohydrate ratio cal­cu­la­tions). Dein­ten­sification/depre­scrib­ing refers to de­creas­ing the dose or fre­quen­cy of ad­min­is­tra­tion of a treat­ment or dis­con­tin­u­ing a treat­ment al­to­geth­er. ADL, ac­tiv­i­ties of daily liv­ing.

†Con­sid­er ad­just­ment of A1C goal if the pa­tient has a con­di­tion that may in­ter­fere with ery­thro­cyte life span/‍turnover.

Sodi­um-Glu­cose Co­trans­porter 2 In­hibitors

Sodi­um-glu­cose co­trans­porter 2 inhibitors are ad­min­is­tered oral­ly, which may be con­ve­nient for older adults with di­a­betes; how­ev­er, long-‍term ex­pe­ri­ence in this pop­u­la­tion is lim­it­ed de­spite the ini­tial efficacy and safe­ty data re­ported with these agents. In pa­tients with es­tab­lished atheroscle­rot­ic cardiovas­cu­lar dis­ease, these agents have shown cardiovas­cu­lar benefits (44).

In­sulin Ther­a­py

The use of in­sulin ther­a­py re­quires that pa­tients or their care­givers have good vi­su­al and motor skills and cog­ni­tive abil­i­ty. In­sulin ther­a­py re­lies on the abil­i­ty of the older pa­tient to ad­min­is­ter in­sulin on their own or with the as­sis­tance of a care­giv­er. In­sulin doses should be titrat­ed to meet in­di­vid­u­al­ized glycemic tar­gets and to avoid hy­po­glycemia. Once-‍daily basal in­sulin in­jec­tion ther­a­py is as­so­ci­at­ed with min­i­mal side ef­fects and may be a rea­son­able op­tion in many older pa­tients. Mul­ti­ple daily in­jec­tions of in­sulin may be too com­plex for the older pa­tient with ad­vanced di­a­betes com­pli­ca­tions, life-‍lim­it­ing co­ex­ist­ing chron­ic ill­ness­es, or lim­it­ed func­tion­al sta­tus. Fig­ure 12.1 pro­vides a po­ten­tial ap­proach to in­sulin reg­i­men sim­plification.

Other Fac­tors to Con­sid­er

The needs of older adults with di­a­betes and their care­givers should be eval­u­ated to con­struct a tai­lored care plan. Im­paired so­cial func­tioning may re­duce their qual­i­ty of life and in­crease the risk of func­tion­al de­pen­den­cy (45). The pa­tient’s liv­ing sit­u­a­tion must be con­sid­ered as it may af­fect di­a­betes man­age­ment and sup­port needs. So­cial and in­stru­men­tal sup­port net­works (e.g., adult chil­dren, care­tak­ers) that pro­vide in­stru­men­tal or emo­tion­al sup­port for older adults with di­a­betes should be in­cluded in di­a­betes man­age­ment dis­cussions and shared de­ci­sion mak­ing.

Older adults in as­sist­ed liv­ing fa­cil­i­ties may not have sup­port to ad­min­is­ter their own med­i­ca­tions, where­as those liv­ing in a nurs­ing home (com­mu­ni­ty liv­ing cen­ters) may rely com­plete­ly on the care plan and nurs­ing sup­port. Those re­ceiv­ing pal­lia­tive care (with or with­out hos­pice) may re­quire an ap­proach that em­pha­sizes com­fort and symp­tom man­age­ment, while de-‍em­pha­siz­ing strict metabol­ic and blood pres­sure con­trol.