Table 3.

Overview of Main Findings from Studies That Evaluated Adverse Events of T2D Medications as a Treatment-Related Attribute

Indicator Influenced	Study (Author, Year)	Treatment Studied	Main Finding
WEIGHT CHANGE
Initiation	Chen et al, 202025	Injectable	37.4% cited being “worried about AEs of injection therapy, such as hypoglycemia and weight gain” as a concern regarding initiation of therapy
	Polonsky et al, 201115	QW injectable	55.1% very/extremely likely to be willing to take medication if it “could help you lose weight” (current oral vs injectable users: 44.0% vs 74.1%) and 51.5% if it “could help you to avoid weight gain” (39.3% vs 72.5%)
Adherence	Farmer et al, 200617	OAD	13.9% agree/strongly agree with the belief that taking OADs regularly “would lead to my gaining weight”, the only belief evaluated that was significantly correlated with reduced adherence (Spearman’s r=–0.25; p<0.01) although not significantly correlated with intention to take medication regularly (r=–0.12)
	Flory et al, 201920	Metformin	Under theme of “motivation”: “other benefits” including weight loss (“When I first started taking metformin, I lost about 50 pounds”)
	Gater et al, 202122	GLP-1/GCG RA	16% cited weight loss as a reason for willingness to continue treatment
	Hauber et al, 200921	OAD	Medication-related weight gain 1 of only 2 attributes (including heart attack risk) significantly associated with an increased likelihood of missing/skipping doses; a weight gain of 9.0 kg decreased the rate of likely adherence by 30% (95% CI 29.6, 32.3)
	Spain et al, 201626	Injectable	24% cited AEs (including weight gain) and 19% cited medication concerns (including weight worry) as barriers to adherence
Discontinuation	de Climens et al, 202023	OAD/injectable	18% who discontinued treatment due to side effects did so because of weight gaina
	Sikirica et al, 201724	GLP-1 RA	25% discontinued because treatment “did not help weight loss” and 8% because they “caused weight gain”
	Spain et al, 201626	Injectable	20%/28% cited AEs (including weight gain) and 4%/11% cited medication concerns (including weight worry) as main/contributory reason for discontinuation
GI AEs
Adherence	Farmer et al, 200617	OAD	32.8% agree/strongly agree with the belief that taking OADs regularly “would cause me unpleasant side effects such as feeling sick or bloated”; belief not significantly correlated with intention to take medication (Spearman’s r=–0.12) or adherence (r=–0.08)
	Flory et al, 201920	Metformin	Under theme of “barriers to metformin use”: GI AEs (“The one side effect it gives me which is the runs”)
	Hauber et al, 200921	OAD	Mild stomach upset had no effect on medication adherence
	Huang et al, 202018	Oral/injectable	Under theme “motivation for medication adherence” and subtheme “barriers”: concerns about medication safety including side effects such as GI upset PwD reduced doses to avert side effects (“My stomach got so upset all the time. I got the diarrhea and I just felt better after I cut it off, and I left it at one … ”)
	Spain et al, 201626	GLP-1 RA	6–8% cited GI AEs as a barrier to current therapy
Discontinuation	de Climens et al, 202023	Oral/injectable	18% of PwD discontinuing treatment because of side effects did so because of GI disorders
	Gater et al, 202122	GLP-1/GCG RA	29% reported vomiting and 21% nausea as reasons for being unwilling to continue therapy
	Sikirica et al, 201724	GLP-1 RA	64% discontinued because treatment “made me feel sick” and 45% because they “made me throw up”
	Spain et al, 201626	Injectable	AEs most common reason for discontinuation of liraglutide (32%) and exenatide (23%), with nausea and vomiting the main reasons in liraglutide discontinuers (18%)
HYPOGLYCEMIA
Initiation	Chen et al, 202025	Injectable	37.4% cited being “worried about AEs of injection therapy, such as hypoglycemia and weight gain” as a concern regarding initiation of therapy
	Polonsky et al, 201115	QW injectable	38.5% very/extremely likely to be willing to take medication if “you could have a lower risk of having hypoglycemia”
Adherence	Hauber et al, 200921	OAD	Mild-to-moderate hypoglycemia negatively impacted medication adherence if it occurred >2 times per month
	Huang et al, 202018	Oral/injectable	Under theme of “motivations for adherence” and subtheme “barriers”: concerns about medication side effects such as hypoglycemia impeded adherence
	Sajith et al, 201416	Unspecified	13.3% cited “other factors” including hypoglycemia as affecting medication adherence
	Spain et al, 201626	Injectable	24% cited AEs (including hypoglycemia) as a barrier experienced while on therapy
Discontinuation	de Climens et al, 202023	Oral/injectable	16% of those discontinuing medications because of side effects did so due to hypoglycemiab
	Sikirica et al, 201724	GLP-1 RA	10% discontinued due to “symptoms of low blood sugar”
	Spain et al, 201626	Injectable	20%/28% cited AEs (including hypoglycemia) as the main/contributory reason for discontinuation

Notes: ^a6.2% in whole study population; ^b5.6% in whole study population.

Abbreviations: AE, adverse event; CI, confidence interval; GI, gastrointestinal; GLP-1 RA, glucagon-like peptide-1 receptor agonist; GLP-1/GCG RA, dual glucagon-like peptide-1/glucagon receptor agonist; OAD, oral antidiabetes drug; PwD, person/people with diabetes; QW, once weekly; T2D, type 2 diabetes.