Hypoglycemia is a common and potentially life-threatening adverse effect of inappropriate diabetes treatment. Typical cardiac complications are ischemia with angina pectoris, myocardial infarction, stroke and arrhythmias, such as atrial fibrillation (AF), ventricular tachycardia and heart failure. Elderly multimorbid patients with type 2 diabetes and polypharmacy and/or cardiac autonomous neuropathy represent a very high risk group for cardiovascular complications associated with hypoglycemia. Targets for glycemic control have to be adapted to the risk of hypoglycemia with a priority of stable glucose homeostasis without rapid fluctuations. Elderly patients with diabetes have a >20% risk of AF. At blood glucose levels of <3 mmol/l with a duration of >30 min, prolongation of QTc time and ventricular tachycardia occur with an increased risk of ventricular fibrillation and sudden death. Ventricular arrhythmias and AF significantly increase mortality in patients with heart failure. Rapid fluctuations with a mean amplitude of glucose excursion (MAGE) >5 mmol/l promote vulnerability of electrical stability of the heart, particularly in frail patients with preexisting coronary heart disease and autonomic neuropathy. Antihyperglycemic agents, such as metformin, acarbose and sodium glucose cotransporter 2 (SGLT2) inhibitors have only a low risk of severe hypoglycemia. Dipeptidyl peptase 4 (DPP-IV) inhibitors and glucagon-like peptide 1 (GLP1) analogues as insulin secretagogues have a lower risk for hypoglycemia than sulfonylurea and insulin. Early basal insulin treatment in patients insufficiently controlled with metformin is efficient, safe and convenient. Targets for glucose control and HbA1c have to be individualized and the choice of drugs must be risk-adjusted. Risk of hypoglycemia should be used as guide in decision-making for safe treatment of diabetes.