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)
Pa­tient characteristics/‍­­­­­health sta­tus	Healthy (few co­ex­ist­ing chron­ic ill­ness­es, in­tact cog­ni­tive and func­tion­al sta­tus)
Rea­son­able A1C/­treat­ment goal	A1C <7.5% (58 mmol/‍mol)
Ra­tio­nale/­considerations	Pa­tients can gen­er­al­ly per­form com­plex tasks to main­tain good glycemic con­trol when health is sta­ble Dur­ing acute ill­ness, pa­tients may be more at risk for ad­min­is­tra­tion or dos­ing er­rors that can re­sult in hy­po­glycemia, falls, frac­tures, etc.
When may reg­i­men sim­pli­fi­ca­tion be re­quired?	If se­vere or re­cur­rent hy­po­glycemia oc­curs in pa­tients on in­sulin ther­a­py (even if A1C is ap­pro­pri­ate) If wide glu­cose ex­cur­sions are ob­served If cog­ni­tive or func­tion­al de­cline oc­curs fol­low­ing acute ill­ness
When may treat­ment de­intensification/­de­pre­scrib­ing be re­quired?	If se­vere or re­cur­rent hy­po­glycemia oc­curs in pa­tients on nonin­sulin ther­a­pies with high risk of hy­po­glycemia (even if A1C is ap­pro­pri­ate) If wide glu­cose ex­cur­sions are ob­served In the pres­ence of polyphar­ma­cy
Pa­tient characteristics/‍­health sta­tus	Complex/‍intermediate (mul­ti­ple co­ex­ist­ing chron­ic ill­ness­es or 21 instrumen­tal ADL im­pair­ments or mild-‍tomoderate cog­ni­tive im­pair­ment)
Rea­son­able A1C/­treat­ment goal	A1C <8.0% (64 mmol/‍mol)
Ra­tio­nale/­considerations	Co­mor­bidi­ties may af­fect self-‍man­age­ment abil­i­ties and ca­pac­i­ty to avoid hy­po­glycemia Long-‍act­ing med­i­ca­tion for­mu­la­tions may de­crease pill bur­den and com­plexity of med­i­ca­tion reg­i­men
When may reg­i­men sim­pli­fi­ca­tion be re­quired?	If se­vere or re­cur­rent hy­po­glycemia oc­curs in pa­tients on in­sulin ther­a­py (even if A1C is ap­pro­pri­ate) If un­able to man­age com­plexity of an in­sulin reg­i­men If there is a sig­nif­i­cant change in so­cial cir­cum­stances, such as loss of care­giv­er, change in liv­ing sit­u­a­tion, or fi­nan­cial dif­fi­cul­ties
When may treat­ment deintensification/‍­de­pre­scrib­ing be re­quired?	If se­vere or re­cur­rent hy­po­glycemia oc­curs in pa­tients on nonin­sulin ther­a­pies with high risk of hy­po­glycemia (even if A1C is ap­pro­pri­ate) If wide glu­cose ex­cur­sions are ob­served In the pres­ence of polyphar­ma­cy
Pa­tient characteristics/‍­health sta­tus	Com­mu­ni­ty-‍dwelling pa­tients re­ceiv­ing care in a skilled nurs­ing fa­cil­i­ty for short-‍term re­ha­bil­i­ta­tion
Rea­son­able A1C/­treat­ment goal	Avoid re­liance on A1C Glu­cose tar­get:100–200 mg/dL (5.55–11.1 mmol/‍L)
Ra­tio­nale/­considerations	Glycemic con­trol is im­por­tant for re­cov­ery, wound heal­ing, hy­dra­tion, and avoid­ance of in­fec­tions Pa­tients re­cov­er­ing from ill­ness may not have re­turned to base­line cog­ni­tive func­tion at the time of dis­charge Con­sid­er the type of sup­port the pa­tient will re­ceive at home
When may reg­i­men sim­pli­fi­ca­tion be re­quired?	If treat­ment reg­i­men in­creased in com­plexity dur­ing hos­pi­tal­iza­tion, it is rea­son­able, in many cases, to re­in­state the prehos­pi­tal­iza­tion med­i­ca­tion reg­i­men dur­ing the re­ha­bil­i­ta­tion
When may treat­ment deintensification/‍ de­pre­scrib­ing be re­quired?	If the hos­pi­tal­iza­tion for acute ill­ness re­sulted in weight loss, anorex­ia, short-‍term cog­ni­tive de­cline, and/‍or loss of Glu­cose tar­get: phys­i­cal func­tioning
Pa­tient characteristics/‍­health sta­tus	Very com­plex/poor health (long-‍term care or end­stage chron­ic ill­ness­es or moderate-to-se­vere cog­ni­tive im­pair­ment or 2+ ADL de­pen­den­cies)
Rea­son­able A1C/treat­ment goal	A1C <8.5% (69 mmol/)†
Ra­tio­nale/­considerations	No ben­e­fits of tight glycemic con­trol in this pop­u­la­tion Hy­po­glycemia should be avoid­ed Most im­por­tant out­comes are main­te­nance of cog­ni­tive and func­tion­al sta­tus
When may reg­i­men sim­pli­fi­ca­tion be re­quired?	If on an in­sulin reg­i­men and the pa­tient would like to de­crease the num­ber of in­jec­tions and fin­ger­stick blood glu­cose mon­i­tor­ing events each day If the pa­tient has an in­con­sis­tent eat­ing pat­tern
When may treat­ment deintensification/‍­de­pre­scrib­ing be re­quired?	If on nonin­sulin agents with a high hy­po­glycemia risk in the con­text of cog­ni­tive dysfunc­tion, de­pres­sion, anorex­ia, or in­con­sis­tent eat­ing pat­tern If tak­ing any med­i­ca­tions with­out clear ben­e­fits
Pa­tient characteristics/‍health sta­tus	Pa­tients at end of life
Rea­son­able A1C/­treat­ment goal	Avoid hy­po­glycemia and symp­tomat­ic hy­per­glycemia
Ra­tio­nale/­considerations	Goal is to pro­vide com­fort and avoid tasks or in­ter­ven­tions that cause pain or discom­fort Care­givers are im­por­tant in pro­vid­ing med­i­cal care and main­taining qual­i­ty of life
When may reg­i­men sim­pli­fi­ca­tion be re­quired?	If there is pain or discom­fort caused by treat­ment (e.g., in­jec­tions or fin­ger­sticks) If there is ex­ces­sive care­giv­er stress due to treat­ment com­plexity
When may treat­ment deintensification/‍­de­pre­scrib­ing be re­quired?	If tak­ing any med­i­ca­tions with­out clear ben­e­fits in im­prov­ing symp­toms and/‍or com­fort